草药S108联合丹参抑制大鼠同种肾移植慢性排斥与bFGF、PDGF、TGF-β的表达关系

Anti-chronic-rejection effects of S108 in combination with Chinese medicine Danshen in rat renal allograft

目的研究草药S108,丹参对抗慢性排斥的作用以及与细胞因子PDGF、bFGF、TGF-β在移植肾中表达变化的关系。方法建立同种异体肾移植模型。实验分组:A组给予小剂量CsA(1.5mg/kg/d)作为对照组;B、C、D组在用小剂量CsA的同时,分别给予丹参、S108以及S108联合丹参。术后8、12周时测定移植肾功能并作形态学检查,免疫组织化学方法检测细胞因子PDGF、bFGF、TGF-β的表达。结果各组均有不同程度的慢性排斥反应包括肾小球硬化、肾小管萎缩、慢性血管硬化和肾间质纤维化,(A>BorC>D;B,C,DGroupsVSGroupA,P<0.05;B,CGroupsVSGroupD,P<0.05;BGroupsVSGroupC,P>0.05。)并伴有Bun、血Cr增高(A>BorC>D;B,C,DGroupsVSGroupA,P<0.05;B,CGroupsVSGroupD,P<0.05;BGroupsVSGroupC,P>0.05。)同时,移植肾组织细胞因子(PDGF、BFGF、TGF-β)的表达水平增高。(A>B>C>D;B,C,DGroupsVSGroupA,P<0.05;B,CGroupsVSGroupD,P<0.05;BGroupsVSGroupC,P<0.05。)结论S108及丹参有一定防治慢性排斥的作用,二者合用效果优于单独用药。细胞因子(PDGF、bFGF、TGF-β)在移植肾慢性排斥、功能下降甚至失活的过程中有重要作用。S108联合丹参有一定的拮抗上述因子的效应,这可能是其对抗慢性排斥的作用机制。

Objective In this research, we investigate the anti-CR effect of three different therapies： S108, Chinese medicine Danshen and S108 in combination with Chinese medicine Danshen. To explore their anti-CR effects and the underlying mechanism, the CR-medel in rat renal allograft was established, the expression levels of some important cytokines（PDGF, bFGF, TGF-β） were examined, and the morphology changes of the renal allografts were assessed. Methods Kidney transplantation was performed from rat Lweis to ACI（allogenic） according to Fabrea and Kamada 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（1.5mg/ 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）, S108（5g/kg/d） and S108 in combination with Chinese medicine Danshen. Renal function and morphology changes were assessed at 8, 12 week after transplantation. All sections of kidney grafts were studied by immunohistochemistry and cytokines（PDGF,bFGF,TGF-β） were measured. Results All renal grafts have variable degrees of CR, which consists of tublar atrophy, interstital fibrosis, glomerulosclemsis 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〈0.05; B Groups VS Group C, P〈0.05.） Companied with the mentioned changes, serum Bun 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〉0.05.） Meanwhile, levels of the expression of cytokines （PDGF, bFGF, TGF-β） were 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〉 0.05）. Conclusions The results showed that S108 and Chinese medicine Danshen had some certain effects on the prevention and treatment of CR. And when beth of them were used together, the therapy was proved more effective. Moreover, The results also suggested that cytokines（PDGF, bFGF, TGF-β） play a very important role in CR as well as renal aUografts dysfunction or loss. And we found that the expression levels of these and cytokines can be decreased to certain degree by S108 in combination with Chinese medicine against CR.