Clinical Therapeutic Research On Decanta And Disintoxication Treating Hemorrhage Stroke With Yang Symptom-complex And Neuroprotective Mechanism

BackgroundAccording to the investigation of cause of death from National Ministry of Public Health,the stroke(acute cerebrovascular disease)has already become the secondary cause of death of our population in continuous five years.At present,stroke is "the important killer" seriously jeopardizing mankind healthy,with clinical features of "four high and one low"—high disease incidence,case fatality,mutilation rate,recurrence rate and low recovery rate.Currently,the domestic and overseas organizations have made much more progressions in ischemic cerebrovascular disease and accumulated plenty of remedy experience.However,these research organizations have made less advancements about intracerebral hemorrhage. Traditional Chinese medicine plays an important role in our national health care system and a great quantity of clinical researches have confirmed that traditional Chinese medicine has better curative effect and potency in the remedy of intracerebral hemorrhage.So bringing superiority of traditional Chinese medicine into full play and choosing suitable traditional Chinese medicine are extremely necessary to degrade case fatality,mutilation rate of intracerebral hemorrhage.Those measures are accepted by he human being gradually.In recent twenty years,plenty of clinical practices have certificated that fu-sthenia syndrome is a common syndrome of stroke in the acute stage. The pathogenesis of stroke about "the fu-sthenia syndrome","the endogeny poison","poison damaging brain collaterals" has been thought highly of by many scholars and has become focal points of approach.By means of recognition of etiopathogenisis and pathogenesis of stroke and study of symptom-complex,we propose new medicative thought of applying decanta and disintoxication in the strok acute stage.We consider that decanta and disintoxication(we adopt capsule tongfuxingshen and capsule yinaomai to treat disease,and these two capsules have been developed by professor Liu Maocai of traditional hospital of Guangdong province according to his plenty of clinical practice,and these two capsules play an important role in decanta and rouse,breaking sputum and having one's ideas straightened out,remove obstacles from porus sudoriferus)can elevate clinical therapeutic efficacy of stroke.PurposeThe clinical research makes use of capsule tongfuxingshen and capsule yinaomai to treat acute hemorrhage stroke patients with yang symptom-complex on the basis of previous study of capsule tongfuxingshen and capsule yinaomai and pathogenesis of "during the disease of stoke, sputum,stagnant blood persists all the time and fu-sthenia syndrome,poison circulates as cause and effect".We adopt multidimensional stroke curative effect evaluation system and objectively evaluate curative effect of decanta and disintoxication treating acute hemorrhage stroke patients with yang symptom-complex.Aspect of empirical study,we appraise the rat model from the point of view of ethology,symptom-complex,microcosmic indicatrix and drug treatment to aim directly at yang symptom-complex on the basis of previous study of combination rat model of hypertensive intracerebral hemorrhage disease and yang symptom-complex.We study combination rat model's expression abnormality of nuclear factorκB(NF-κB),inhibitor of NF-κB(IκB)and tumor necrosis factor-α(TNF-α)mRNA,intercellular adhension molecule-1(ICAM-1)mRNf in order to research the influence of capsule tongfuxingshen and capsule yinaomai and the effectiveness of resisting neurocyte apoptosis of these two capsules.We try our best to annotate decanta and disintoxication's possible neuroprotective mechanism of action to treat acute hemorrhage stroke patients with yang symptom-complex from the point of view of inflammatory reaction.MethodDuring the clinical research,we choose acute hemorrhage stroke patients with yang symptom-complex as investigation objects and carry out prospective randomized controlled trial.According to experimental group: control group=1:1 amounting to 60 cases,we obtain randomized numbers by means of pems3.1 edition statistics software.After sieve,we undertake simple randomization according to the time of patient stay,give western medical symptomatic treatment plus traditional Chinese medicine treatment and simple western medical symptomatic treatment respectively.In detail, by means of the outcome of traditional Chinese medicine treatment and simple western medical symptomatic treatment,we analyze the influence of decanta and disintoxication with regard to acute hemorrhage stroke patients with yang symptom-complex's traditional Chinese medicine symptoms and signs accumulated points,neurologic impairment degree accumulated points,daily life capability,existence quality,and approach rule of traditional Chinese medicine's differentiation of symptoms and signs step by step.The trial has been carried out according to strict test requirement.Finally we collect 60 cases of particular disease totally and experimental group and control group has no deletion.During the experimental research,we randomize 150 Sprague-Dawley(SD)rats as A simple disease group(hypertensive intracerebral hemorrhage group),B combination of disease and syndrome group (hypertensive intracerebral hemorrhage disease and yang symptom-complex),C treatment group(hypertensive intracerebral hemorrhage disease and yang symptom-complex plus medicinal treatment group),D normal control group. We appraise the rat model from the point of view of signs and symptoms,neural functional assessment,cerebral histopathology,cerebral moisture capacity,microcosmic indicatrix and drug treatment to aim directly at yang symptom-complex.We choose five time point—6h,12h,24h,48h,72h after rat operation on brain,detect NF-κB,IκB's activity and apoptosis of right caudate nucleus of rat brain tissue with immunohistochemical method, determine expression diversity of TNF-αmNNA,ICAM-1mRNA with hybridization in situ,observe and evaluate the influence of decanta and disintoxication. Statistical analytical method:measurement data is indicated with(?)±s. Group comparisons deploy t-test/analysis of variance and heterogeneity of variance adopts Keuskal-Wallis.Numeration data's group comparisons deploy chi square test.P＜0.05 indicates that difference has statistical significance, and we apply SPSS13.0 statistical software.OutcomeClinical research:Two groups' common data of prior treatment including years of age,sex,previous cerebral apoplexy history,National Institute of Health Stroke Scale(NIHSS),stroke's signs and syndromes of traditional Chinese medicine are compared.The outcome shows difference has no significance(P＞0.05).Analysis of data manifests that two groups' basal line of prior treatment has elementary coincidence and comparability.At the time point of 3d,7d,14d,28d after treatment and follow-up 90d,we appraise NIHSS),signs and syndromes of traditional Chinese medicine(including serious degree of symptom and influence of life). At the time point of 14d,28d after treatment and follow-up 90d,we appraise barthel index(BI)and quality of life index(QLI).Consequences indicate:â‘ The difference of two groups'NIHSS has no significance(P＞0.05)at the time point of 3d,7d and has significance(P＜0.01)at the time point of 14d,28d and 90d.These hint that curative effect of treatment group is better than control group and that treatment prescription of traditional Chinese medicine differentiation of symptoms and signs can ameliorate patients' neurologic impairment of 14d,28d and 90d.â‘¡The difference of two groups' serious degree of symptom has no significance(P＞0.05)at the time point of 3d and has significance at the time point of 7d,14d,28d and 90d(P＜0.05 or P＜0.01).The difference of two groups' influence of life has no significance(P＞0.05)at the time point of 3d,90d and has significance at the time point of 7d,14d and 28d(P＜0.01).These illustrate that curative effect of treatment group is better than control group and that treatment prescription can mitigate traditional Chinese medicine symptoms and signs at the time point of 7d,14d,28d,90d after treatment.â‘¢The difference of two groups' BI has no significance(P＞0.05)at the time point of 14d,28d and has significance(P＜0.05)at the time point of 90d.These explain that treatment prescription of traditional Chinese medicine differentiation of symptoms and signs can strengthen life viability of follow-up 90d and degrade serious mutilation rate of follow-up 90d.â‘£The difference of two groups' QOL has no significance(P＞0.05)at the time point of 14d,28d and 90d.But we can see that treatment prescription of traditional Chinese medicine differentiation of symptoms and signs can reinforce tendency of patients' survival quality and that with the prolongation of follow-up time,the difference of two groups' QOL becomes more significant.Empirical study:After hypertension and cerebral hemorrhage operation, the rats of A-C groups become agitated,irritable,dizzy,thirsty,dry stool, hypertensive and have cephalophyma,cerebral edema and neurologic defect signs.Compared with normal control group,the levels of A-C groups' serumal T and E₂ step down and the levels of A-C groups' serous PR-A,Angâ…¡and ALD step up(P＜0.05 or P＜0.01).Compared with B combination of disease and syndrome group,brain tissue damage and neurologic impairment of C treatment group have been mitigated.All of these above-mentioned symptoms and signs and biochemical indicators of C treatment group have been ameliorated obviously(P＜0.05 or P＜0.01).After cerebral hemorrhage operation,activities of NF-κB,IκB and TNF-αmRNA,ICAM-1mRNA of right caudate nucleus of rat brain tissue obviously step up at the time point of 6h,12h,12h respectively,and achieve peak at the time point of 12h,24h,48h respectively,and still higher than normal control group at the time point of 3d(P＜0.05 or P＜0.01).Time course change of apoptosis has fundamental coincidence with expression of NF-κB.At the time point of 6h after rat operation on brain,IκB's activity becomes fall-off and reaches the lowest point at 12h and gradually return to the level of 6h.At every time point,capsule tongfuxingshen and capsule yinaomai can depress activities of NF-κB,IκB and TNF-αmRNA,ICAM-1mRNA and decrease neuron apoptosis and increase IκB's expression(P＜0.05 or P＜0.01).ConclusionThe randomized controlled trial of decanta and disintoxica-tion treating acute hemorrhage stroke 60 patients with yang symptom-complex indicates that treatment prescription of traditional Chinese medicine differentiation of symptoms and signs can ameliorate patients'neurologic impairment with statistical difference at the time point of 7d,14d,28d after treatment,can mitigate traditional Chinese medicine symptoms and signs at the time point of 7d,14d,28d,90d after treatment,can strengthen life viability of follow-up 90d and ease handicap,can reinforce tendency of patients' survival quality with the prolongation of follow-up time.Empirical study indicates that the method of establishing rat model relatively is in line with the theory of traditional Chinese medicine etiopathogenisis and pathogenesis of yang symptom-complex,the model formation procedure also gets close to clinical process of occurrence development of hypertensive cerebral hemorrhage.That is to say,hepatic and renal yin deficiency,hyperactivity of liver-yang,sputum and heat fu-sthenia syndrome,qi and blood reversing,straightly invading the brian, blood flowing over outside of vessel.Cerebral histopathology,neural functional assessment and biochemical indicators manifest that the rat model has the basic features of hypertensive intracerebral hemorrhage disease and yang symptom-complex of mankind and can partly simulate etiopathogenisis,pathogenesis and morbidity characteristic of hypertensive intracerebral hemorrhage disease and yang symptom-complex of mankind. The outcome of immunohistochemical method indicates that decanta and disintoxication can regulate down endonuclear NF-κB's activity in the rat model brain tissue,can reinforce cytoplasmic IκB's activity.The outcome of apoptosis shows that decanta and disintoxication can decrease TUNEL positive cells expression in the rat model brain tissue.The outcome of hybridization in situ manifests that decanta and disintoxication can inhibit expression of TNF-αmRNA,ICAM-1mRNA at transcriptional level.So we suppose that decanta and disintoxication may bring about therapeutical effect to brain injured by means of inhibiting IκB's reduce,NF-κB's excess activation,regulating down generation,release of many inflammation mediators such as TNF-α,ICAM-1,mitigating or discontinuating inflammation cascade reaction,decreasing apoptosis aim at the purpose of protect neurocytes.All of these have provided experimental bases in order to spread application of decanta and disintoxication during the stroke acute stage.