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Experimental Study Of Protective Effect Of Sivelestat Sodium On The Rat Intracerebal Hemorrhage (ICH)

Posted on:2006-01-13Degree:MasterType:Thesis
Country:ChinaCandidate:Q LiuFull Text:PDF
GTID:2144360155951202Subject:Pharmacology
Abstract/Summary:PDF Full Text Request
Intracerebral hemorrhage(ICH) is a common mutiple disease. The related data show that : hemorrhagic cerebral apoplexy takes 10%~25% of all kinds of cerebral apoplexies;among all the cerebrovascular diseases,the disease incidence of intracerebral hemorrhage takes the toppest position,which is 1.8%~11% with direct case fatality rate 38%~43% and invalidity rate 70%~80%.This disease is quite common among the old,and it is generally happened in the more aged people and suffer higher case fatality rate .Generally,one-year older in age means 3.47 times in case fatality rate. In China ,the annual ICH incidence is approximately 120~180 persons per 100,000 with annual 1,300,000 new cases and 1 million death , Especially,half of these patients died within two days .The depravation of the disease is usually related to the energy metabolic disorder of peripheral tissues of cerebral edema ,inflammatory response, hematoma triggered by ICH as well as the injury of oxygen free radical and some studies showed that polymorphonuclear neutrophil elastase(NE) play a key role in the injury after ICH.At present,medical conservative treatment and surgical operation are adopted as to ICH. Sivelestat sodium cultivated by Japan is a micromolecular NE inhibitor,which can inhibit NE conversely and competitively, It has been proved by clinical research that sivelestat sodium can improve respiratory function of acute lung injury(ALI) sufferers accompanied by systemic inflammatory response syndrome(SIRS) through inhibiting NE. Its chief mechanism is likely that: directly inhibit NE synthesis and discharge ;reduce the injury of bronchoa epithelia and vascular endotheliua conducted by activated neutrophils;decrease the permeability of vascular endothelia and reduce the discharge of thrombaxane as well as the permeability of pulmonary arterial pressure and lung ;inhibit the production of human macrophages and inflammatory cytokines as IL-1b,IL-6,TNF-α etc.There has been a report from abroad that sivelestat sodium can improve cerebral edema,cerebral injury and inflammatory response caused by cerebral Ischemia-Reperfusion. By analyzing the effect mechanism of sivelestat sodium and the pathologic & physiologic mechanism of ICH combined with the previous research results,we may be assume that sivelestat sodium bears the protective function of ICH. The objective of the research is to investigate the protective effect of sivelestat sodium on the rat ICH induced by collagenase as well as to have a preliminary probe on the mechanism . Methods: to adopt nucleus caudatus microinjection of collagenase inducing rat ICH model,to observe the effect of sivelestat sodium on the ICH rat ethologic change, pathologic change of cerebral tissues in thehemorrhagec side and the change of brain water content as well as the effect on TNF-a express change in the hemorrhagec side ,permeability change of BBB and the change of SOD,MDA,MPO content. Result and conclusion: 1. Sivelestat sodium(150mg/kg) can promote the recovery process of ICH rat ethologic change induced by collagenase; It can lessen the occurrence of cerebral edema and display the phonomenon of dose dependency. Meanwhile, sivelestat can lessen the pathologic change of ICH rat hemorrhagic side ,showing that sivelestat has the protective function ofn rat ICH caused by collagenase. 2. Sivelestat sodium(150mg/kg) can decrease the rising degree of BBB permeability in the hemorrhagec side of ICH rats induced by collagenase;It can prevent the reduction of SOD content as well as the increase of MDA content in the hemorrhagic side of ICH rats induced by collgaenase .It can decrease TNF-a express as well as the rising of MPO content in the hemorrhagic side of ICH rats induced by collagenase ,showing that sivelestat sodium is likely to bear the protective function on ICH rats induced by collagenase by means of protecting BBB of ICH rats,promationg tissues' clearance of free radical as well as the anti-aggregation of polymorphonuclear leukayte and the discharge of inflammatory medium.
Keywords/Search Tags:ICH, sivelestat sodium, collagenase
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