Ding Huiyn (丁輝燕), Deng Lijun (鄧立軍), Hn Yufu (韓裕富)

a. Department of Neurology, Wuhan 6th Hospital, Wuhan 430015, China

b. Department of Neurology, 2nd Affiliated Hospital of Army Medical University, Wuhan 400000, China

ABSTRACT OBJETTIVE: To observe the effects of Yinxingdamo Injection combined with oxiracetam capsule on cognitive function and neurological deficit in patients with acute cerebral infarction. METHODS: A total of 76 patients with acute cerebral infarction were randomly divided into observation group and control group, with 38 patients in each group.Patients in the control group were treated with conventional western medicine and oxiracetam capsules while patients in the observation group were given Yinxingdamo injection intravenous drip treatment on the basis of the same treatment. After 4 weeks of treatment, the cognitive function of the two groups before and after treatment was observed [Simple Intelligence Scale (MMSE Score), Montreal Cognitive Assessment Scale (MoCA Score)], Neurological Deficit [Chinese Stroke Scale(CSS Score), Daily Life Activity ability (ADL score)], free radical biochemical indicators [malondialdehyde (MDA), oxide dismutase (SOD)] changes, and statistical effects of two groups. RESULTS: After treatment, the total effective rate of the observation group was 92.1%, which was significantly higher than 73.7% of the control group (P ＜ 0.05). The MMSE score and MoCA score of the two groups were significantly increased after treatment (P ＜ 0.05), and the MMSE score and MoCA score inobservation group were significantly increased after treatment than the control group (P ＜ 0.05). The CSS scores of the two groups were significantly decreased after treatment (P ＜ 0.05), and the ADL scores were significantly increased(P ＜ 0.05). The improvement of CSS score and ADL score in the observation group were significantly better than those in the control group (P ＜ 0.05), and serum MDA levels were significantly decreased in both groups after treatment (P ＜ 0.05),and SOD levels were significantly increased (P ＜ 0.05), and the improvement of MDA and SOD levels in the observation group was significantly better than that in the control group group (P ＜ 0.05). CONCLUSION: Yinxingdamo injection combined with oxiracetam capsule can effectively inhibit the oxygen free radical reaction injury in patients with acute cerebral infarction, and significantly improve the symptoms of cognitive dysfunction and neurological deficit in patients.Its curative effect is exact and worthy of clinical application.

KEYWORDS: Acute cerebral infarction; Yinxingdamo injection; Oxiracetam capsule; Cognitive function;Neurological deficit

Acute cerebral infarction, also known as acute ischemic stroke, mainly refers to cerebral stenosis caused by cerebral stenosis and thrombosis, resulting in focal acute cerebral insufficiency or even complete interruption, brain tissue ischemia and hypoxia and softening necrosis, In turn, a series of clinical syndromes of focal neurological symptoms appear[1]. The disease is a common type of stroke. The onset of acute disease is rapid, the condition changes rapidly, and the focal neurological deficit reaches a peak within a few minutes to several hours. If the treatment is not timely, many neurological deficits are easily left. Cognitive dysfunction such as memory loss, aphasia, and decreased computing power seriously affects patients' physical health and quality of life[2,3]. Acute cerebral infarction often causes extensive ischemic necrosis of brain tissue, but there are still a large number of surviving neurons in the peripheral ischemic penumbra. Clinical studies have shown that timely establishment of the blood circulation pathway in the penumbra around the cerebral infarction lesion has important clinical significance for the rescue of reversible impaired neurons, improvement of neurological deficits and cognitive dysfunction[4].

At present, Western medicine provides thrombolytic therapy for patients with acute cerebral infarction who are in the thrombolysis time window and meet the thrombolysis indications. For those who are beyond the thrombolysis time window or have thrombolysis contraindications, they mainly use neuroprotective agents and anticoagulation methods. But because the western medicine treatment mechanism is relatively simple, the prognosis of patients is not very satisfactory, only a small part of the body function of the survivors can be fully restored. Therefore, finding a more effective treatment for acute cerebral infarction has become a thorny issue in clinical research.

In recent years, the integration of traditional Chinese and Western Medicine has gradually become a new development direction of clinical treatment in acute cerebral infarction. A variety of proprietary Chinese medicines have been applied in the clinical adjuvant treatment of acute cerebral infarction. The treatment has multiple effects, pathways and target characteristics.Complex pathophysiological features of acute cerebral infarction. Yinxingdamo Injection is a traditional Chinese Medicine compound preparation, which has the functions of dilating cerebral blood vessels, increasing blood supply to brain tissue, improving red blood cell deformability,reducing blood viscosity and improving blood rheology[5],which has a definite therapeutic effect on this disease.From January 2017 to January 2018, the author used Yinxingdamo Injection combined with western medicine oxiracetam capsules to treat 38 patients with acute cerebral infarction, and achieved satisfactory results. The report is as follows.

CLINICAL INFORMATION

General information

A total of 76 patients with acute cerebral infarction admitted to our hospital during the above period were selected. The diagnosis of Western medicine complies with the provisions of the Guidelines for the Diagnosis and Treatment of Acute Ischemic Stroke in China 2010[6]:① rapid onset; ② focal neurological function Defects;③ clinical symptoms maintained for several hours; ④brain CT confirmed responsibility for cerebral infarction lesions. TCM syndrome differentiation is in line with the provisions of the "Diagnostic and Efficacy Evaluation Standards for Stroke" on qi deficiency and blood stasis syndrome[7]: the eyes are skewed, the words are sloppy, the body is not squat, the body is abnormal, the complexion is white, the shortness of breath is weak, the tongue and veins shows that the tongue is dull, the tongue is greasy, the tongue has scalloped marks, and the veins are fine. The patients were 18 to 70 years old, with the first onset, with a course of ＜ 72 h, confirmed by CT and MRI scans, and with 5 points ＜ NIHSS score ＜ 25 points.Patients needed to sign informed consent. Exclusion of large-area cerebral infarction, hemorrhagic cerebral infarction, brain stem infarction, cerebellar infarction and multiple cerebral infarction, acute cerebral infarction caused by brain tumor, brain trauma, brain parasitic disease, heart disease, metabolic disorders, etc, and patients with major organ dysfunction, combined with severe systemic or local infections and bleeding tendency,with aphasia or severe cognitive impairment, pregnancy,lactation and mental illness.

The enrolled patients were randomly divided into 2 groups: 38 patients in the observation group, 25 males and 13 females; aged 40-70 (55.7±3.8) years; duration 5-35(9.5±1.2) h; infarction site: 22 cases of basal ganglia, 9 cases of temporal lobe, 5 cases of parietal lobe and 2 cases of frontal lobe. There were 38 patients in the control group,24 males and 14 females; age 40-68 (55.9±3.7) years; the course of disease was 6～38 (9.9±1.3) h; the infarction site: 21 cases of basal ganglia, 10 cases of temporal lobe,parietal lobe 6 cases, 1 case of frontal lobe. There were no significant differences in gender, age, disease duration and infarction between the two groups (P ＞ 0.05).

Clinical methods

Both groups of patients were given routine medical treatment, including reducing blood pressure, blood sugar,maintaining water and electrolyte balance. Thrombolytic therapy for those who were in the thrombolysis time window and in compliance with thrombolytic indications,and oral aspirin lowering blood lipids and anti-platelet aggregation, intravenous edaravone scavenging free radicals; subcutaneous injection of low molecular weight heparin for anticoagulation. If necessary,intravenous drip of mannitol reduced intracranial pressure. The control group was treated with oral oxiracetam capsules (Hunan Jianlang Pharmaceutical Co., Ltd., Guoji Zhunzi H20030037, specification:0.4g) on the basis of conventional treatment, 0.8g/time,3 times/d, for 4 weeks. On the basis of the control group,the observation group was given Yinxingdamo Injection(Tonghua Guhong Pharmaceutical Co., Ltd., National Drug Standard H22026140, Specification: 5 mL) for treatment. Take 20 mL and add 250 mL 0.9% normal saline to intravenous drip, once a day, and 4 weeks as a course of treatment for a total of 1 course of treatment.

Clinical Index

Clinical efficacy

According to the reference[8]to develop evaluation criteria. ① Basic recovery: after treatment, NDS functional deficit score decreased more than 90%,disability level was 0, daily work and housework were basically unaffected; significant progress: after treatment,NDS functional defect score decreased by 46%-90%, sick level was 1-3, part of patients can take care of themselves.Progress: after treatment, NDS functional defect score decreased by 18%-45%, invalid: after treatment, NDS functional defect score decreased less than 18%, and even decreased more. Basic recovery + significant progress +progress = total effective. ② Cognitive function assessment:Using the Simple Intelligence Scale (MMSE score) and the Montreal Cognitive Assessment Scale (MoCA score)to assess the improvement of cognitive function before and after treatment, the MMSE score is 0-30 points,the higher the score, the recognition The stronger the knowledge, the 30 points of the MoCA scale, 26 points or more are normal, 18 to 26 are classified as mild cognitive dysfunction, 10 to 17 are moderate cognitive dysfunction,and less than 10 are severe cognitive function. obstacle.③ Assessment of neurological deficits: the Chinese stroke scale (CSS) was used to assess the improvement of neurological deficits before and after treatment. The main components were composed of 7 dimensions, with a score of 45. The higher the score, the more serious the neurological deficit was. ④ Assessment of daily living ability: using the Activity of Daily Living (ADL) scale to assess the improvement of self-care ability before and after treatment, including 10 dimensions, out of 100 points, the higher the score, the ability to self-care The stronger. ⑤ Free radical biochemical indicators:taking 3 mL of fasting peripheral venous blood before and after treatment. After centrifugation, the level of malondialdehyde (MDA) was detected by thiobarbituric acid colorimetric method, and superoxide was detected by chemical colorimetry. Disprolinease (SOD) levels are strictly in accordance with the actual and manual instructions.

Statistical methods

Statistical analysis was performed using SSPS 22.0 statistical software. Measurement data were expressed asand t-test was used for comparison. The counting data is represented by n (%), and the comparison is performed by the X2test. P ＜ 0.05 was considered statistically significant.

RESULTS

Comparison of clinical effects after treatment in 2 groups

After treatment, the total clinical efficacy rate of the observation group was 92.1%, which was significantly higher than that of the control group (73.7%) (P ＜ 0.05).See Table 1.

Comparison of MMSE score and MoCA score before and after treatment in 2 groups

Before treatment, there was no significant difference between the two groups in MMSE score and MoCA score(P ＞ 0.05). After treatment, the MMSE score and MoCA score of the two groups were significantly increased(P ＜ 0.05), and the MMSE score and MoCA score of the observation group were observed. The scores in observation group were significantly higher than that of the control group (P ＜ 0.05). See Table 2.

Comparison of the degree of neurological deficit and daily living ability before and after treatment in 2 groups

Before treatment, there was no significant difference in CSS scores and ADL scores between the two groups(P ＞ 0.05). After treatment, the CSS scores of the two groups were significantly decreased (P ＜ 0.05), and the ADL scores were significantly increased (P ＜ 0.05).and the improvement of CSS score and ADL score in the observation group were significantly better than the control group (P ＜ 0.05). See Table 3.

Table 1. Comparison of clinical effects after treatment in 2 groups (%)

Table 2. Comparison of MMSE score and MoCA score before and after treatment in 2 groups , scores)

Table 2. Comparison of MMSE score and MoCA score before and after treatment in 2 groups , scores)

Note: ① compared with before treatment, P ＜ 0.05; ② compared with the control group, P ＜ 0.05.

Table 3. Comparison of CSS scores and ADL scores before and after treatment in 2 groups scores)

Table 3. Comparison of CSS scores and ADL scores before and after treatment in 2 groups scores)

Note: ① Compared with that before treatment, P ＜ 0.05; ② Compared with the observation group, P ＜ 0.05.

Table 4. Comparison of MDA levels and SOD levels before and after treatment in 2 groups

Table 4. Comparison of MDA levels and SOD levels before and after treatment in 2 groups

Note: ① compared with before treatment, P ＜ 0.05; ② compared with the control group, P ＜ 0.05

Comparison of MDA and SOD levels before and after treatment in 2 groups

Before treatment, there was no significant difference in serum MDA and SOD levels between the two groups (P ＞ 0.05). After treatment, the serum MDA levels of the two groups were significantly decreased(P ＜ 0.05), and the SOD level was significantly increased(P ＜ 0.05), and the improvement of MDA and SOD levels in the observation group were significantly better than that in the control group (P ＜ 0.05). See Table 4.

DISCUSSION

Acute cerebral infarction refers to a disorder in the blood supply to the brain. The blood flow is suddenly reduced or even completely interrupted, causing damage to the local brain tissue due to ischemia and hypoxia, and then a series of cerebrovascular diseases with symptoms of neurological deficits. In recent years, the clinical morbidity rate of acute cerebral infarction has increased significantly in China, and it has become one of the main causes of death in China, which seriously threatens people's life health and safety[9].

The pathogenesis of this disease is very complex,involving endometrial damage, hemorheological abnormalities and hemodynamic abnormalities. Common risk factors include coronary heart disease, hypertension,diabetes, hyperlipidemia and obesity, mainly due to the brain. Atherosclerosis leads to stenosis or occlusion of the cerebral artery, rupture of the plaque to form a thrombus,and the new collateral circulation has not been established in time or the establishment of a new collateral circulation is not ideal, resulting in a significant lack of cerebral circulation reserve capacity. In addition, in addition, after the occurrence of acute cerebral infarction, damaged neuronal cells will release a large number of free radicals, which will further damage brain tissue. SOD and MDA are important indicators reflecting the level of oxygen free radicals in the body. SOD is an antioxidant enzyme substance mainly derived from animals, plants and microorganisms, and has the effect of scavenging free radicals. MDA is a membrane lipid peroxidation reaction, and an important product that has the effect of aggravating oxidative cell membrane damage.

Clinical studies have confirmed that after hypoxicischemic necrosis of brain tissue in patients with acute cerebral infarction, brain cells are often in a state of stress,which stimulates the production of free radicals, and the activity of SOD is significantly reduced, resulting in a significant decline in the function of scavenging free radicals. The dynamic balance of oxidation and anti-oxidation in the body has been broken, further aggravating the condition of ischemic cerebrovascular disease[10].

At present, thrombolysis is the first choice for clinical treatment of acute cerebral infarction, which can quickly improve the clinical symptoms of patients, but thrombolytic therapy has strict time window limitation,and simple thrombolytic therapy can not completely prevent the complex pathophysiological changes of cerebral infarction. Therefore, the administration of other drugs to adjuvant therapy is of great significance for improving clinical efficacy and reducing complications.Oxiracetam capsule is a pyrrolidone derivative, which can effectively promote the synthesis of phosphorylcholine and phosphorylethanolamine, thereby activating adenosine triphosphate in brain tissue, promoting circulation metabolism of brain tissue, and improving the utilization of glucose and oxygen in brain tissue,significantly improving neuronal cell damage and cognitive dysfunction after cerebral infarction.

In recent years, Chinese medicine has been increasingly used in the adjuvant treatment of acute cerebral infarction. Acute cerebral infarction belongs to the category of "stroke" in traditional Chinese medicine.Traditional Chinese medicine believes that stroke is the standard of virtual standard and the evidence of Shang Shengxia. The performance is the yin and yang bias. The standard is qi and blood disorder, and its incidence is in the body and blood. On the basis of internal deficiency,factors such as fatigue, anger, anxiety, alcohol and tobacco, etc., lead to qi and blood rebellion, visceral disorders, and sinful accumulation in the brain, causing cerebral vasospasm and disease.It can be seen that due to the deficiency of phlegm and blood stasis is the root cause of stroke, blood stasis and collaterals are the key pathogenesis of stroke, and the treatment should adopt the new method of promoting blood circulation and removing blood stasis. Yinxingdamo Injection is a commonly used cardio-cerebral vasodilator in clinical practice. It has dilated cerebral vascular and coronary blood vessels,improved memory decreasing caused by cerebral ischemia and cognitive dysfunction[11]. The main component is total flavonoids of Ginkgo biloba extract, terpenoids(ginkgolide, bilobalide) and dipyridamole. The role of Ginkgo biloba in cardiovascular and cerebrovascular diseases has been clarified, and its protective effect on the nervous system mainly related to its strong antioxidant function. Modern pharmacological studies have shown that total flavonoids of Ginkgo biloba have increased blood flow to the brain, regulated vascular tone and high permeability of pathological capillaries, inhibited platelet activating factor activity, fought atherosclerosis, combated cellular lipid peroxidation, and increased resistance.Oxidative capacity, memory enhancement and sensory function, delaying the development of dementia[12,13].

In addition, ginkgo flavonoids is a widely used free radical scavenger, which can effectively protect nerve cells from free radical damage, and can reduce vascular resistance and improve cerebral vascular microcirculation.Ginkgolide A-C is a natural strong antagonist of platelet activating factor, which can effectively dilate blood vessel caliber, resist platelet aggregation, inhibit thrombosis,and thus protect glial cells and microvessels[14].Ginkgolide is effective in protecting neuronal cells of the central nervous system from damage during the ischemic period. Dipyridamole has a significant inhibitory effect on platelet aggregation in vivo. When it reaches 50ug/mL, it can not only effectively fight platelet release,but also exert strong antagonistic effect on various phosphodiesterase components, and finally achieve endothelial protection, relief of vasospasm and inhibition of thrombosis.

Pharmaceutical research shows that the total flavonoids, ginkgolide, bilobalide and dipyridamole of Ginkgo biloba can be greatly enhanced when they are used in a certain proportion, and the drug toxicity is not significantly increased. Sun Zhihua[15]confirmed that Yinxingdamo injection combined with ozagrel can effectively improve the symptoms of hemorheology and neurological deficits in patients with ischemic stroke. Wu Guolong et al[16]confirmed that Yinxingdamo injection is effective in the treatment of acute cerebral infarction and has a significant effect on secondary prevention of ischemic stroke.

The results of the study showed that the total effective rate of the observation group after treatment was significantly higher than that of the control group,cognitive function (MMSE score and MoCA score),neurological deficit (CSS score and ADL score), and free radical biochemical indicators (MDA and SOD).The improvement was significantly better than the control group. It is suggested that Yinxingdamo Injection combined with oxiracetam capsule can effectively inhibit the oxygen free radical reaction damage in patients with acute cerebral infarction, significantly improve the symptoms of cognitive dysfunction and neurological deficit in patients. The curative effect is exact and is worthy of clinical application.