| Objective: Although treatment of acute rejection episodes in renal transplantation has advanced short-term survival in the majority of cases, there is not yet satisfactory for the long-term effect. Later renal allograft dysfunction caused by immunological and nonimmunological mechanisms remains the major obstacle to long-term survival .Its precise mechanism is very likely complex and unclear in details. The chronic vascular rejection(CVR) cause the lumenal stenosis gradually and the ischemia and anoxia of microcirculation .which play the important role in later renal dysfunction. Unfortunately, we currently lack effective preventive or therapeutic strategies for this long-term deterioration. Therefore ,basing on our pervious observations, we investigated the treatment and the mechanisms of tow Chinese medicines ant-CVR: Chinese Herb-S and Ligustrazine as well as both of them were used together.Methods: Total of 65 SD closed colony strain rats as well as Wistar strain rats were used in this experiment. Kidney transplantation was performed from SD to Wistar strain(allogeneic)according to procedure of Fabre with some modification. Depending on the different given medicine, all of experimental rates were divided into five groups, including GroupA,B,C,D and E. GroupE(n=5) as controls were not treated withmedicine and group D(n=10) received low-dose CsA(1.5mg/kg/day)alone. The other groups (group A,B,C)were receive Ligustrazine, Chinese Herb-S plus Ligustrazine, and MMF combined with CyclosporineA respectively. Renal funtion and resultant morphology changes were assessed at 4,8,and 12weeks after transplantation. All sections of kidney grafts were stained with monoclonal antibodies such as MHC-II ,LFA-1 ,ICAM-1 ,IgG, TGF-P ,PDGF and bFGF; Positive cell counts were expressed as mean盨 of cells/field of view (C/FV);Results: The kidney grafts were developed glomerular lesions consisted with glomerulosclerosis and chronic vascular rejection as well as extensively interstitial fibrosis by treating with low-dose Cyclosporine A in group D. Companied with increased serum Bun and SCr(vs. Groups B and C.p<0.05) .Recipient's mean of survival time was lower than other groups(over 84 days of groups A.B,and C; P<0.05). Meanwhile levels of cytokines and adhesion molecules expression in groups D were significantly increased(vs.group B,C;p<0.05). In groups B and C. Expressions of cytokines, adhesion molecules and infiltrate cells were reduced, compared with the groups A and D(p<0.05).In remarkable contrast with other groups, both groups B and C have shown only minimal changes in glomerulosclerosis and arteries (arterial obliteration <25%),and their serum levels of Bun and SCr are less than the other groups (p<0.05).However, there was no significant difference between group B and groupC on the aspects of their function ,morphology changes, and CVR grade.Conclusion: Various risk factors involved in immunological and nonimmunological lesions lead to the renal vascular endothelium cells injury which triggers the chronicvascular rejection(CVR) by Cytokine-adhesion molecule cascade. The CRV is a irreversible process which cause the lumenal stenosis gradually ,and ischemia and anoxia of the microcirculation as well as the later renal dysfuntion. Thus we here affirming that prevention of immunological and nonimmunological mechanism in the early-stage is a key step. The effect on treatment of CVR with Chinese Herb-S plus Ligustrazine is satisfactory, and more effective than the treatment of CVR with Ligustrazing alone. These results strongly suggest that Chinese Herb-S and Ligustrazine may down-regulate the expression of cytokines and adhesion molecules such as MHC- II ?LFA-LICAM-LIgG, TGF-P ,PDGF and bFGF. inhibit the movement and infiltration of inflammation cells, protect the vascular endothelium cells of transplantation kidney, reduce platelet aggregation as well as improvemicrocirculation of renal grafts. When both of them were used together they were proved to be more effective in pr...
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