| BACKGROUNDAcute intracerebral hemorrhage (AICH) is one of life-threaten diseases. The AICH morbidity rate is very high in China. The studies are very limited all over the world. There is not systematic 5 clinical study in AICH therapeutic time window and the animal experiment only lies the beginning stage. OBJECTIVETo study the possible therapeutic time window (TTW) of AICH, and the intervention of Zhongfengxingnao oral liquid (ZFXN) to AICH TTW. 10 METHODS(1) Systematically summarizing "Stroke Core Pathogenesis Theory " of Professor Chen Shaohong.(2) Clinical Study:(1)Retrospectively analyze the two AICH randomized clinical trail from1988-2003, sub-groups differentiating according the time from onset to the first treatment. (2)We15 divided into 0-6h, 6-24h, 24-48h, 48-72h, the baseline date include sex, age, blood pressure, medical history scale, concomitant disease scale, Glasgow Coma Scale (GCS), National Institute of Health Stroke Scale (NIHSS). (3)The endpoints include mortality rate, NIHSS, Glasgow Outcome Scale (GOS), Barthal Index (BI), and Multiple Regression Analysis on Effect factors of 90d BI Improvement. (4)Analyze the hematoma enlargement after ZFXN treatment. (3) Neuron20 Culture Study:(1)We adopt cerebrospinal fluid (CSF) pharmacology and primary neuron culture experimental methods, culturing the cerebral cortex neuron of SD rats by Beagle dog CSF containing the ZFXN in vitro, (2)making AICH cell model in vitro by thrombin and ischemic & hypoxia combinational injure to neuron (TIH model), (3)screening the optimal dose of herbal CSF via MTT assay method.(4)6,12,24,48, 72 hrs after TIH injured, MTT assay to analyze the25 mitchondria metabolism, Fura-2/AM loaded cells of TIH injured neuron by double wavelength fluorescence to detect the cytosolic free Ca2+ ([ Ca2+]i), propidium iodide (PI) dying the model neuron by flow cytometry to analyze the apoptosis of the neuron after AICH. RESULTS:(1) "Stroke Core Pathogenesis Theory " is based on as whole disease, including deficient30 Original Qi as root, Phlegm and Blood Stasis as indirect pathological product caused by deficient original Qi, Wind and Fire are the final pathogenic factors, So recovering the Original Qi and restoring consciousness, removing the Blood Stasis and resolving Phlegm, dispelling Fire and subduing Wind are the treatment rules. (2)Clinical study æ¼Total patient sample is 367, including 187 ZFXN and 181 control, (2)in the baseline data have not significant difference between ZFXN35 and control group except systolic blood pressure (SBP), diastolic blood pressure (DBP) and meanarterial pressure (MAP) of 48-72H. (3) In the time window from 0 to 72hrs, ZFXN was able to decrease the mortality rate of 30 and 60d, improve the BI of 90d. In the time window from 48 to 72hrs, ZFXN was able to decrease the mortality rate of 60d, improve the BI of 90d. (4)ZFXN was able to decrease the prothrombin time (PT), no evidence showed that ZFXN was able to increase 5 the hematoma enlargement. (5) The treatment selection and baseline NIHSS are the effect factors of 90d BI (P<0.05) . The therapeutic time window from 0 to 72hrs have not significant effect on the 90BI (PX).05). (3) Neuron Culturing Studyåº TIH cell model fits in the pathophysiological changes after AICH, which is a optimal cell model to study AICH in vitro, (2)herbal CSF containing ZFXN can protect neuron, the optimal dose is 20% CSF in low dosage group. (3)10 From 0 to 72hrs after AICH, the mitchondria metabolism capability, lactate dedydrogenase (LDH) revealing, neuron apoptosis have changes curve, [ Ca2+]/ overload happened from 0 to 48hrs after AICH. (4)The ICH intervention time window of ZFXN including, the optimal effect to enhance the mitchondria metabolism capability lies in 0-6 hrs, and have effect from 0-72hrs. the optimal effect of decreasing the LDH revealing is from 48 to 72 hrs, and have effect from 0 to 72hrs. the15 optimal inhibiting the[ Ca2+]i overload is 0 to 24hrs, and a... |
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