Study Of Influence Factors On Cerebral Hemorrhage And Yang Syndrom Combination And Initial Establishment Of Its Corresponding Animal Model

BackgroundStroke is one of the leading causes of mortality and chronic disability worldwide and the mortality of cerebral hemorrhage is farthur higher than one of cerebral infarction.Effect of Traditional Chinese Medicine(TCM)has been proved reliable for prevention and treatment of cerebral hemorrhage.Yang syndrome and Yin syndrome's standard of differentiation in the acute stage of hemorrhage stroke was put forward in the national key technologies R&D program of 10th five years that was Clinical trial and evaluation on comprebensive treatment on attack in acute stage of stroke.The standard was proved feasible and the patients with Yang syndrome account for morn than 80%of all in acute stage of cerebral hemorrhage.Influential action of constitution,chronic diseases ect are very important in TCM Differential Diagnostics.Study on influencing factors is indispensable for Yang syndrome and Yin syndrome's standard of differentiation in the acute stage of hemorrhage stroke.On the other hand,animal models used in TCM treating stroke could not simulate TCM features.It is essential to make animal models of combining disease and TCM syndrom on cerebral hemorrhage.ObjectiveThe study was distributed into two parts that the first part was clinical part and the second was experiment Yang syndrome and Yin syndrome's standard of differentiation in the acute stage of hemorrhage stroke.The first part of study proposes to preliminaryily investigate influential action of the factors such as age,gender,body shaping,past history on the standard of differentiation in the acute stage of hemorrhage stroke.The first part of study objects to establish a animal model of cerebral hemorrhage and Yang syndrom combination based on the past clinic and experiment trials.Besides, the mechanism was explored of Tongfu Xingshen capsule and Yaonaomai capsule treating Yang syndrome in the acute stage of hemorrhage stroke.MethodClinical data of 404 cases of hemorrhage stroke was analyzed retrospectively in the clinical research based on the program of 10th five years.Firstly,relationship of the influencing factors and Yang syndrome and Yin syndrome of differentiation was single factor analyzed such as age,gender,body shaping,past history and course of disease.Secondly, multivariate analysis of the factors was carried out by logistic regression analysis in SPSS13.0.All rats were divided randomly into eight groups,that is group A(cerebral hemorrhage group),group B(Fu Shi syndrom group),C(heat syndrom group), D(Yang syndrom group),E(cerebral hemorrhage and Yang syndrom combination group),F(treated group),G(control group),and H(sham operation group)in the experiment reserch.The group B,C,D models were produced respectively by administrating Compound Diphenoxylate Tablets,warm heat herbs,Compound Diphenoxylate Tablets and warm heat herbs.The group A and E models were induced respectively by injecting collagenase in two-kidney two-clip renovascular hypertensive rats,combining model-estambalishing means of group A with goup D.Group F was administrated Tongfu Xingshen capsule and Yaonaomai capsule.The models were evaluated by recording mortality of rats,observing symtoms and physical signs,scoring neurological deficits,observing brain pathomorphological features and ultrastructure,measuring the contents of warter,micro indexes correlating syndroms and syndrome testing by Chinese herbal complex treatment.The micro indexes correlating syndroms include hemorheology.Heme oxygenase-1(HO-1)expression was measured with immunohistochemistry,HO-1mRNA expression was detected with in situ hybridization histochemistry at different time points(12,24,48,72 and 168 h) after cerebral hemorrhage.ResultLogistic regression analysis of clinical research showed that patients with more than 60 years old acounted for 57.1%(P＜0.05),and male patients did 66.3%(P＜0.01)in ones with Yang syndrome.The odds ratio values of age and gender respectively 0.468,0.495.The regression coefficient values of age,gender and consciousness respectively -0.760,-0.704. In the experiment reserch,the mortality of group E rats is 23.3 percent without significant difficiency with sham group(P＞0.05),and the evaluation system of the integrated cerebral hemorrhage and Yang syndrom animal model were established initially.The evaluation system included indexes correlated with disease,TCM syndromes,microcosmic.①The evaluation system indexes correlated with disease of the integrated cerebral hemorrhage and Yang syndrom animal model were established initially.The model rats of group E showed obviously high blood pressure,hemorrhagic brain injury such as brain edema etc,neurological deficits such as paralysia.Their brain pathomorphological and ultrastructure features paralleled with ones of cerebral hemorrhage,lt was concluded that syndroms and brain pathomorphological features observed in the integrated disease and syndrome model ones of clinical syndroms of hypertensive cerebral hemorrhage patients.②The evaluation system indexes correlated with TCM syndromes of the integrated cerebral hemorrhage and Yang syndrom animal model were established initially.It were displayed in rats of group E that symptoms or signs such as dysphoria and aggression,pink eye, thirsty,dry stool and dark red tongue.The strenthened metabolism was a pathology feature of its tongue.The appearances were reduced after treating. It was proved that TCM syndroms observed in the integrated disease and syndrome model were similar to ones of clinical TCM syndroms of cerebral hemorrhage patients with Yang syndrome.③The evaluation system micro indexes of the integrated cerebral hemorrhage and Yang syndrom animal model were established initially.In model rats of group E,all indexes of hemorheology highened campared with sham group(P＜0.05 or P＜0.01).We concluded that the integrated disease and syndrome model was provided with TCM syndroms such as heat,Yin deficiency and Yang hyperactivity,sputum and stagnated blood.Tongfu Xingshen capsule and Yinaomai capsule were proved to improve all evaluation indexes which displayed the integrated cerebral hemorrhage and Yang syndrom animal possesed features of Yang syndrome in testing syndrome by Chinese herbal complex treatment.The two capsules could up-regulate expression of HO-1 protein and mRNA in the rat' s brain tissue and they was markedly increased at 12 hour point,and reached the peak value at 48 hour point.ConclutionAbove all,influencing factors of Yang syndrome syndrome in the acute stage of hemorrhage stroke were age and gender.Female and more than 60 years old were protective factors.On the other hand,the integrated cerebral hemorrhage and Yang syndrom animal model could simulate etiology,pathogenesis and clinical syndroms characters of hypertensive intracerebral hemorrhage with Yang syndrom.The model is worth to be generalized widely.