Xifeng Phlegm And Blood Stasis Mechanism For The Treatment Of Cerebral Hemorrhage

1.Purpose1.Intracerebral hemorrhage(ICH) is one of the common cerebrovascular disease. Itwas paid close attention because of its serious invalidity and high mortality. This assay review the treatments for acute intracerebral hemorrhage of the modern medicine and traditional Chinese medicine.Based on the theories about apoplexy in traditional Chinese medicine(TCM) and modern medicine and the viewpoint of Professor Shizaixiang,to make preliminary discussion of pathogenesis and treatment of acute ICH. 2.Using collagenase-insected model of intracerebral hemorrhage to investigate the effects of Linghuang decoction on improving brain edema, blood rheology, reducing free radical damage,inflammatory reaction, pathological structural changes as well as the safety of application of removing blood stasis drugs during cerebral hemorrhage. 3. Through clinical research to discuss the curative effect of of Lingyang Gouteng decoction in acute cerebral hemorrhage treatment.2.Method2.1. Experiment researchIntracerebral hemorrhage (ICH) was induced by injecting collagenase into rat caudate nucleus according to Rosenberg method1.The SD rats were radomly divided into 6 groups: sham, model , LingHuang with small,middle,big dosage and NaoxueKang. Measure the dynamic changes of neurological defect, brain water content, blood rheology,cerebral hemorrhage volume of each group at corresponding times ( 3d,7d ).2.Determine free radical level, inflammation respond, cerebral hemorrhage quantity in brain tissue of each group in the 3d time.3. Observe pathological changes of each group ( HE dyeing, electron microscope), to apply Perls ' reaction to ditermine the iron ion content in brain tissue of each cerebral hemorrhage rat group (sham,model, Lingyang, naoxuekang group), to apply immunhistochemical reaction to determine the dynamic expression of AQP4 and MMP9 in brain tissue of each rat ICH group at correspondingtimes( 1d, 3d, 7d).4. RT-PCR to detect AQP4mRNA and MMP9mRNA expression in brain tissue of each rat ICH group .2.2.Clinical researchTo apply radomised control reaserch to appraises the clinical curative effect of LingJiao Gouteng decoction in cerebral hemorrhage treatment. The 60 acute ICH patients were radomly divided into a treatment group and a control group ( each 30 examples).Control group was given conventional western therapy, treatment group based on this conventional therapy was given LingJiao Gouteng decoction。To adopt neurological defect grade and NIHSSS grade to give a neurological function mark at hospitalized and 30d after that; Using BI to to give a life capability mark after 30d treatment. To measure blood pressure, blood sugar and blood lipid as major observation indeces. At the same time to observe side effect occured during treatment process .3 . Result3.1 . Experiment research31.1 . At 3d, aggregation index of red blood cell, the whole blood and plasma viscosity increased, deformation index of red blood cell decreased, brain water content increased,neurological defect symptoms appeared in the ICH rat in model group. LingHuang Tang and NaoxueKang obviously reduced red blood cell aggregation index, whole blood viscosity, plasma viscosity, whole blood and the viscosity of blood plasma, increased the deformation ability of red blood cell, reduced brain water content,and reduced neurological defect symptoms.3.1.2 . SOD activity, CAT activity , GSH activity in brain tissue of ICH rats were obviously decreased, MDA content was apparently increased.It is said that during ICH process,the free oxygen radical- cleaning function of major active enzymes were obviously decreased. Oxidized products were apparently increasesed. LingHuang Tang and Nao xue Kang obviously raised the brain tissue SOD activity and reduced the content of brain organization MDA. Linghuang Tang with small dosage increased GSH activity.MPO and TNF-αcontents in brain tissue of ICH rats were increased. It is said that white blood cell infiltration and TNF-αare involved in the pathology process cerebral hemorrhage. Linghuang decoction with middle dosage could reduce TNF-αcontent. This experiment did not show Linghuang decoction and Naoxue Kang influence hemorrhage process.3.1.3 .Electron microscope showed that in model group brain tissue had intrastructure: neuron, microvessel were obviously damaged. In comparison with the model group, Linghuang group and naoxuekang group had less damages. HE dyeing showed evident hematoma at the center, blood was infiltrated to around brain tissue, with different level of oedema. In comparison with model group,treatment group had apparently smaller pathological changes. In model group Fe iron ion and MMP-9 express were arisesed. Linghuang decoction reduced the IOD value of MMP-9 in 3d time. In sham-operation group, there was AQP-4 express.In model group AQP-4 expresses in uptrend, obviously in 1d-3d period. Linghuang decoction and Naoxue Kang reduced AQP-4 express area in 3d time.3.1.4 . In ICH model group, MMP9mRNA and AQP4mRNA express were increased. Linghuang decoction obviously reduced MMP9mRNA, but to reduced AQP4mRNA express unobviously. Naoxue Kang obviously reduced AQP4mRNA expresses, but reduced MMP9mRNA was unobvious.3.2. Clinical research3.2.1 .In treatment group there were 2 cases basically recovered, 17 obvious effect cases and 7 cases effective, 2 cases had no change, 1 was worsen, 1 case death; In control group there were 4 cases basically recovered, 7 cases with obvious effect and 14 cases effective, 1 case had no change, 2 were worsen, 2 cases were death ( P > 0.05) have no statistic difference.3.2.2 .Comparing before and after treatment,neurological defect scors MESSS and NIHSS in each group were obvious improved( P < 0.01), after treatment, neurological defect scores MESSS and NIHSS of treatment group are better than its of control group( P< 0.05).These results indicated that lingyangGouteng tang can improve thepatients' symptoms and signs remarkably,reduce neurological defect.4.Conclusion:1. LingHuang decoction can improve free oxygen damage, improve blood rheology, improve microcirculation, alleviate brain oedema, improveme neurological defect, promote hematoma absorption and reduce TNF-αcontent in brain tissue of ICH rats.2 .Linghuang decoction can improve brain infrastructure damage of ICH rats.3. Linghuang decoction can alleviates brain oedema possibly through reducing MMP9 and AQP4. It reduces MMP9 and MMP9mRNA express be better than that of Naoxue Kang, but reducing AQP4 and AQP4mRNA express is not as good as Naoxue Kang 4. LingJiao Gouteng decoction has definition clinical value for acute cerebral hemorrhage treatment with obvious curative effect and improve prognosis of ICH patient , therefore deserving to further study.