Exper Imental Study On Mechenism For Matrix Degradation Of Liver Fibrosis

Animal experiment has proved that liver fibrosis and cirrhosiscan completely or partly reverse. The nimal model can fully reflectthe Process of matrix degradation, so it is useful to Study themechenism of matix degradation. The development of liver fibrosis isa dynamocal process including not only synthesis and secretion ofECM, but also its degradation and absorption. Relative data indicatesthat MMP and TIMP involve the degradation of matrix in thedevelopment of liver fibrosis. The research of their dynamic changesin the liver fibrosis reversal will be an important theoretical foundationclarifying mechenism of matrix degradation and therapy ofantifibrosis. Here is our experiment:1. The dynamic pathologic observation.Afrter rat models of different stage liver fibrosis were establishedwith CCL₄, the liver fibrosis recovered spontaneously. The liverspecimens were stained with haematoxylin-eosin and observed at thedifferent time phases of reversal. In the reversal process, firstly thehepatocyte degeneration and necrosis were obviously reduced; thenthe active mesenchymal cells (hepatic stellate cells, oval cells), andmature mesenchymal cells (fibroblasts) were evidetly regressed.Finally, as the fibrotic septa were gradually degradated, only a feWfragments of fibers remained. Meanwhile, liver lobular architectureaPPeared recOnStrUction along with the deghation of liver fibrosis, inWhich liver Wes wer fused togethr and became "an lmp wtlha lObule", and reped hePatOcytes aPProached tO theirmathe and hed orderly -- in focal area. The resultsWest tha liver fibrosis and thesis can comletely or partlyreverse in architeta and function.2' The Wc stUdy on MT,M W eXPression.MTlun mRNA was detected by in situ hthedhaon tOinvestigate wr,-MMP mRNA dynthec exPression in thedevelOPmen of lha fibrois and durin the reversal of liver flbrosis.The reSults indicated tha MTlM M was H Mssed inmesenchymal cells (e.g. hePac stellate cells), aiso in partS ofhePatOCyts. The levels of MT,un InRNA exPrssion werHly inCreased in the devebo of liver fibrosis and graduallydecreased tw its remal' The Wssion of MT,^MMP may playan W role in the deVfoPmen oflha fibrosis and itS reversal.3. The tw StUdy on na exPreion.To StUdy N dyndric exPession in the reved of liverfibrosis, ns-l, -2 PrOteins and xlmRNA Were detectedby taohistochendsny, in sita hybridiZation and wianalsis. The results shOWed tha the levels ofna-1, -2 Protethe andoo- lrnRNA exPrssion wer graduall decreased in the reversal ofmild liver fibrosis, bu were firstiy inCrased then decreased twreversal of the heaVy one' Thcy wer W Wssed in hopatocytsnear the wt of fibrotic op and mesW cells. We believetha M may be an pe faCtO in the revend of liver fibrosis.MesenchyInaI cells (e.g. hePac stellate cells) play an rolein the deVfoPwt of lha fibrosis. Weveq it may be tha "SPeCial"hapatocytes and mesenChyInal cells wot togh durin its reVed.We studied the na and MT,-MMP WA dynndc6Mssbo in the reversal of llver fibrosis, after sucessfuly establishedthe reVend Mls of lnd fibrosis and cforsis. MeWle thedyndric pathologi Ms was observed in detail. It will be usefulfor further investigation on ilver fibrosis StUdy...