Anti-chronic-rejection Effects Of Herb-S And Chinese Medicine Danshen In Rat Renal Allograft

Objcc~ive: Although the introduction of Cyclosporine A has greatly increased short-term renal allograft survival, the long-term effect is not yet satisfactory. Chronic rejection (CR) remains the major obstacle to long-term survival of renal allograft, and its exact mechanism is unclear in details. Recent studies have shown that various events including imrnunlogic and nonirnrnunologic factors may contribute to CR, causing later renal allograft dysfunction and loss. However, no effective therapy for CR is yet available. Therefore, it is significant to search for some effective and hypotoxic drugs in great source of Chinese medicine for the treatment of CR. In this research, based on our previous observations, we continued to investigate the anti-CR effect of three different therapies: herb-S, Chinese medicine Danshen and herb-S in combination with Chinese medicine Danshen. To explore their anti-CR effects and the underlying mechanism, the CR-model in rat renal allograft was established, the expression levels of some important cytokines (PDGF-. bFGF~ TGF- f3 ) and adhesion molecules 76 (CD4 -~ CDS MuG-class II .. JCAM- 1 -~ LFA- 1 -. VCAM- 1) were examined, and the morphology changes of the renal allografts were assessed. Miethods: Kidney transplantation was performed from rat SD to Wistar (allogenic) according to Lee and Fisher methods with some important modification. All experimental rats were divided into four groups due to the different given medicine. Group A, as a CR control, were received low-dose CsA(1 .Smg/kg/d) alone. The other groups(group B,C,D), besides the use of low-dose CsA, were given respectively Chinese medicine Danshen(7g/kg/d), herb-S(5g/kg/d) and herb-S in combination with Chinese medicine Danshen. Renal function and morphology changes were assessed at 8, 12 week after transplantation. The histological diagnosis was made according to the 揃anff Schema?standard. All sections of kidney grafts were studied by inmunohistochernistiy and cytokines (PDGF~ bFGF -. TGF- 13) and adhesion molecules (CD4 CD8 -~ MHC-class II ICAM- 1 .~. LFA- 1~ VCAM- 1) were measured. Positive cell counts were expressed by (mean 眘) in a field of view. Results: All renal grafts have variable degrees of CR, which consists of tublar atrophy, interstital fibrosis, glomerulosclerosis and chronic transplant arteriosclerosis. (A > B or C > D, B, C, D Groups VS Group A, P<0.05; B, C Groups VS Group D, P 0.050 ) Companied with the mentioned changes, serum Bun 77 and Cr increased. (A > B or C > D, B, C, D Groups VS Group A, P<0.05; B, C Groups VS Group D, P~0.05; B Groups VS Group C ,P>0.050 ) Meanwhile, levels of adhesion molecules (CDt. CD8~. MI-IC-class II ICAM- 1 LFA- 1 VCAM- 1) expression were increased (A >BorC > D, B, C, DGroupsVSGroupA,P<0.05; B, CGroups VS Group D, P < 0.05; B Groups VS Group C ,P > 0.05 ) and the expression of cytokines (PDGF bFGF TGF- ~ ) were increased (A > BorC > D B, C, DGroupsVSGroupA,P<0.05; B, C Groups VS Group D, P<0.05; B Groups VS Group C ,P>0.050 ) as well. Con eLision: The results showed that herb-S and Chinese medicine Danshen had some certain effects on the prevention and trea...