| Objective:To Study that if Tongfuxingshen Capsule (abbreviated TFXSTN) Tongfu openedxuanfu treat the acute ischemic stroke, compared with the control group,couldreduce patients' neurologic impairment score, stroke TCM symptom integration,reduce disability, improve the ability to live and the quality of life; Tostudy the effect of TFXSJN on the rats' acute focal cerebralischemia-reperfusion injury in neural protection and the gene expression ofprotein 4 (Aquaporin-4. abbreviated AQP-4) in the nerve cells membrane,further to explore if tongfu opened xuanfu could improve the imbalanceexpression of AQP-4 in the nerve cells membrane of focal cerebralischemia-reperfusion injuried model. To explain the essence of Tongfutreatment on ischemic stroke from the modern scientific micro indicatrix, andthe neural protection mechanisms of tongfu on ischemic stroke on the theoryof xuanfu, to innovate theories of Chinese medicine, to find entry points andblaze new trails for stroke' s modernization study and combination of TCM inclinical basis.Method:1. The theories research:Reviewed the medical history of stroke' s Pathogenesis and Modernrecognition on the pathomechanism of fushi syndrome of acute stroke; Exploredthe neuroprotective mechanism of tongfu treatment on acute stroke; Reviewedthe source of xuanfu theory and xuanfu pathogenesis of stroke. Proposed thattongfu could not only get through the gastrointestinal sthenia syndrome,butalso xuanfu; Explained the effect of AQP-4 in ischemic stroke pathogenesisand try to explore the intrinsic link between xuanfu and channel protein2. Clinical research: A retrospective case-control study was adopted, according to the diagnosis,inclusion and exclusion criteria, included in a total of 60 cases of acuteischemic stroke who hospitalized in one or three department of neurology inGuangdong Provincial Hospital of TCM from April 2005 to March 2007, used TFXSJN(for TFXSJN group) and unused TFXSJN (control group) was 30 casesrespective. Except TFXSJN group using TFXSJN, all patients' treatment wasaccording to the general treatment on acute stroke in Guangdong ProvincialHospital of TCM encephalopathy center. Patients were observed at differenttime points (admission day, treated after 14±3days and 21±3 days),thechange of neurologic impairment score (NIHSS). stroke TCM symptom integration,activities of daily living (BI index), disability (mRS) and Quality of Life(SS-QOL) were observed and completed in cases table. SPSS13.0 for windowssoftware was used for data entry, verification, statistic and analysis.Measurement data between two groups using t-test (homogeneity of variance)or t'test (variance missing). Numeration data between the groups usingchi-square test (Crosstabs).3. Experimental research:180 male Sprague-Dawley rats were randomly divided into 66 who were treatedby TFXSJN (TFXSJN group),66 who were treated by water (model group), 36 withsham-operated and 12 in normal group. TFXSJN and model groups have adoptedthe suture technique in the right middle cerebral artery occlusion (Middlecerebral artery occlusion, abbreviated MCAO), 2 hours later the line was pulledout to implement reperfusion injury. The neurologic impairment score wereobserved at 12 hours ldays, 2days, 3days and 7days after operation andtreatment. The brain water content, infarct volume, optical microscope brainlesion extent were measured at lday, 3days and 7days after theoperation. Fluorescence quantitative RT-PCR technique was used to measure theexpression level of AQP-4 mRNA in the injuried side of rat brain at differenttime points (ischemia-reperfusion injury after 12 hour,lday,2days,3daysand 7days), and compared with that of the contralateral side, sham-operatedgroup and normal group. To observe if TFXSJN Tongfu opened xuanfu treatmentcould regulate the abnormal expression of the gene level. SPSS13.0 for Windowsstatistical software was used for data entry, verification, statistic andanalysis. Measurement data comparison between groups was performed byt-test(homogeneity of variance) or t'-test (variance missing),more groups of two-group comparison using the single factor analysis of variance (ANOVA).Numeration data between the groups using chi-square test (Crosstabs).Results:Clinical research:(1) Baseline data: Except for gastrointestinal sthenia syndrome andyin/yang syndrome, the two groups of patients in terms of gender, age, smoking,alcohol consumption, medical history, diseased region, NIHSS score, strokeTCM symptom integration and Gelashige Coma Scale score (GCS), as compared withno statistical difference (P＞0.05);(2) After treatment: Compared with pretherapy, the NIHSS score and strokeTCM symptom integration of two groups were prominently improved at 14±3days and 21±3 days. But the improvement of stroke TCM symptom integrationof TFXSJN group was superior to that of the control group, the difference wasstatistically significant (P＜0.05);(3) At 21±3 days, TFXSJN group' s BI Index, SS-QOL score were higher,and NIHSS score were significantly lower than that of control group, withsignificant differences (P＜0.05); There were no significant differencebetween two groups' score of mRS at 21±3 days (P＞0.05);(4) Adverse reactions:All patients in the two groups during the treatmenthad no adverse reaction.Experimental research:(1) The effect of TFXSJN on neurologic impairment score: the neurologicimpairment score between model group and TFXSJN had no difference at time ofpulling the line and 12 hours later (P＞0.05); But at lday, 2days, 3days and7days,the neurologic impairment score of TFXSJN group were lower than thatof the model group, with significant differences(P＜0.05 or P＜0.01);(2) The effect of TFXSJN on rat brain water content: after operation,TFXSJN and model group rat brain water content at lday and 3days weresignificantly higher than that of the sham-operated group and normal group,with significantly different (P＜0.01).At 3days, the brain water content wasmaximum, at 7days, the brain water content of four groups had no significantdifference (P＞0.05); Compared to model group, the brain water content at 3daysof TFXSJN group was decreased with significant differences (P＜0.01).Comparedto the normal group, the brain water content of sham-operated group had nodifferences at any point(P＞0.05); (3) The effect of TFXSJN on infarct volume: at iday, the infarct volumeof two groups had no significantly different (P＞0.05), But at 3 days and 7days, the infarct volume of TFXSJN group was significantly lower than thatof the model group, with significant differences(P＜0.01);(4) The effect of TFXSJN on rat brain lesion extent: after treated withTFXSJN, the neuronal degeneration, nerve fibers swelling, infarct area andthe infiltration of inflammatory cells were lighter than that of the modelgroup;(5) The effect of TFXSJNon the expression of AQP-4 mRNA: compared to thecontralateral side, the expression of AQP-4 mRNA of TFXSJN group and modelgroup were increased significantly at 12 hour, peaking at 3 days, withsignificant differences (P＜0.01), returned to normal at 7 days, compared tothe contralateral side, sham-operated group and the normal control groupshowed nosignificant difference (P＞0.05).Compared to the model group, theexpression of AQP-4 mRNA in TFXSJN model group peaking at 2days, it had beenreduced to varying degrees at 3 days, with significant difference (P＜0.05);Conclusion:(1) Clinical research shows that the treatment of TFXSJN Tongfu openedxuanfu on acute ischemic stroke, compared to the control group, can improvestroke patients'with stroke TCM symptom integration and neurologicimpairment score, improve the ability to live and the quality of life, withno obvious side effects. Therefore, Tongfu could be as one of the generaltreatments for acute stroke, appropriate application can improve clinicalefficacy.(2) The aim of Tongfu treating stroke is to opening and regulatingxuanfu, not just to getting through the gastrointestinal sthenia syndrome.Therefore, TFXSJN was used for the stroke patients of non-phlegm-heat fushi,it could serve as a good therapeutic effect similarly. One purpose is to openthe xuanfu, the other is that it can prevent the formation and therapy thefushi syndrome, prevent the aggravation of the patient's condition, fullyembodies the academic thinking of TCM that" following the prognosis of adisease"and "preventing before the disease", which can give good results.(3) Animal experiments shows that TFXSJN Tongfu opened xuanfu will be ableto reduce the focal cerebral ischemia reperfusion injury in cerebral infarctvolume, water content, reducing the brain tissue pathological damage, reducing the neurological deficit score, and play a protective role onischemic neuronal cells.(4) In acute cerebral ischemia-reperfusion injury, there exists aup-regulation of AQP-4mRNA gene expression. It has significantly increasedat 12 hours, peaking at 3days, and returning to normal at 7days. Theup-regulation of AQP-4mRNA expression may be closely related to the ischemicbrain edema formation. TFXSJN can be able to adjust the imbalance expressionof AQP4-mRNA in ischemia-reperfusion injury, reduce ischemic brain edema,which plays a role of neuroprotective effect. Regulation the abnormalexpression of AQP-4mRNA gene may be one of the molecular mechanisms of Tongfuto treat ischemic stroke.(5) TFXSJN Tongfu opened xuanfu to treat focal cerebral ischemia-reperfusioninjury can regulate the imbalance expression of nerve membrane channel protein.Therefore, we presume that there may be some common substance between xuanfuand nerve membrane channel proteins (such as AQP-4.). Connection of Tongfuand the theory of xuanfu and application it to the study of stroke may be helpfulto explain the essence of Tongfu treatment on acute stroke, improve the strokeclinical efficacy and the theories of traditional Chinese medicine and moderninnovation... |
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