扶肾颗粒对腹膜透析相关性腹膜纤维化的影响及其作用机制的实验研究

目的:通过对腹膜透析大鼠进行干预,观察扶肾颗粒对腹膜纤维化相关细胞因子的影响及其作用机制探讨。方法:SPF级健康雄性SD大鼠75只,体重180～200g,适应性饲养1周后,依大鼠体重分层,随机分为:正常对照组(A组,n=15),无任何处理,腹腔注射生理盐水,100ml.kg-1.d-1,连续4周;肾衰5/6切除+1.5%PD组(B组,n=15);肾衰5/6切除+1.5%PD+扶肾颗粒组(C组,n=15);肾衰5/6切除+4.25%PD组(D组,n=15);肾衰5/6切除+4.25%PD+扶肾颗粒组(E组,n=15),除A组外,各组均制成肾衰模型,其中B、C组予腹腔注射1.5%LPDS,100ml.kg-1.d-1,连续4周;D、E组予腹腔注射4.25%LPDS,100ml.kg-1.d-1,连续4周,自透析开始,对C组和E组予灌服扶肾颗粒,以200gSD大鼠计算,灌胃剂量1.8ml/d。其余各组予灌服2ml生理盐水,共灌服4周。观察各组实验动物的大体状态、体重变化、腹膜滤过功能及血清纤维化调控因子表达变化。结果:在治疗4周后,除正常对照组(A组)外,其余各组均体现为负超滤,但是,同浓度透析治疗组中,应用扶肾颗粒干预组其超滤情况明显优于未应用扶肾颗粒组(P<0.05),其作用显著,同时,葡萄糖转运量方面亦体现为相似结果。与正常对照组比较(A组),其余各模型组相关促纤维化因子表达水平均明显升高(P<0.01)。TGF-β1方面,D组的表达水平明显较其他各组升高(P<0.05)。CTGF及IL-6方面,结果与TGF-β1相似。VEGF方面,E组较D组明显降低(P<0.05)。随着透析治疗的进行,HGF与BMP-7表达水平均反应性升高,各模型组二者水平均较正常对照组明显升高(P<0.01)。HGF方面,C组较B组明显升高(P<0.01)。BMP-7方面,E组较D组明显升高(P<0.05)。结论:扶肾颗粒可减轻腹透大鼠的肾功能损伤,保护残余肾功能,改善腹透大鼠的超滤量及葡萄糖转运量,抑制促纤维化因子TGF-β1、CTGF、IL-6、CTGF等表达,调高抗纤维化因子HGF、BMP-7的表达,进而起到抑制腹膜透析相关腹膜纤维化的发生,改善腹膜透析效能。

Experimental Study of the Fushen Granules on Peritoneal Fibrosis Correlating Peritoneal Dialysis and its Mechanism

Objective:To investigate the effect of Fushen granules on peritoneal fibrosis related cytokine.Methods:After one week of adaptive feeding,75 SD rats meeting SPF class were stratified in terms of weight and then randomized into five equal groups:A,blank control group without intervention but 100 ml.g-1.d-1 physiologic saline intraperitoneal injection;B,5/6 nephrectomy +1.5% PD intraperitoneal injection;C,5/6 nephrectomy +1.5% PD intraperitoneal injection + Fushen granules;D,5/6 nephectomy + 4.25% PD intraperitoneal injection;E,5 /6 nephrectomy + 4.25% PD intraperitoneal injection + Fushen granules.The rats in group BCDE have partial nephectomy into kidney failure model.The rats in group B and C were treated with 1.5% LPDS,ip,100 ml.kg-1.d-1;while in group D and E treated with 4.25% LPDS,ip,100 ml.kg-1.d-1 for four weeks.The rats in group C and E were treated with Fushen granules intragastric administration together with peritoneal dialysis for four weeks.The condition of rats including weight,peritoneal filtration and the expression of serum fibrosis regulatory factor were measured.Results:After four weeks of treatment,the rats represent as negative ultrafiltration except group A.The condition of groups treated with Fushen granules were significantly better than the other groups(P < 0.05),while the transportation of glucose was of the similar situation.Compared with group A,the other groups show elevated expression of fibrosis stimulating factors(P < 0.05).The group D expressed more TGF-β1 than the other groups(P < 0.05),while the expression of CTGF and IL-6 show the same results.The group E shows lower VEGF level(P < 0.01) and BMP-7 level(P < 0.05) than group D.The group C expressed more HGF compared with group B(P < 0.05).Conclusion:The burden of renal injury could be reduced and the residual renal function could be protect with Fushen granules,and it could also improve the ultrafiltration and glucose transportation of peritoneum,inhibit the expression of fibrosis stimulatingfactors like TGF-β1、CTGF,IL-6,CTGF,and increase expression of HGF and BMP-7,therefore its anti-fibrosis action would increase the efficacy of peritoneal dialysis.