A Pharmacodynamic Study Of Yishentongluo In Rats With Nephrotic Syndrome And Its Molecular Mechanism

Objective To study the effective mechanism of Yishentongluo on treating rats with nephrotic syndrome and restraining the proliferation in rat mesangial cells.Methods 1.50 rat models made by cationic bovine serum albumin(C-BSA) were devided into five groups at random,including the pathological pattern group,the control group(Shenyansiweipian,SYSW), low-dosage Yishentongluofang(YSTL) group,middle-dosage group,and high-dosage group.Each experimental group consisted of 10 rats and the normal group contained 10 normal rats in the same batch.All rats were examined 24 hours later for urine protein quantity(24huPro),albumin(Alb), serum creatinine(Scr) and blood urea nitrogen(BUN).Their pathological form were also observed and positive area ratio examined.Furthermore, they were examined the distribution and quantity of interleukin-6(IL-6), transforming growth factor-beta 1(TGF-β) and Smad7 with immunohistochemistry in kidney.2.The serum of YSTL was made.With lipase as stimulating factor,the mesangial cells(MC) cultured were divided into five groups,including the control(normal serum),the pathological pattern(lipase,LPS),low-dosage,middle-dosage and high-dosage YSTL group.The proliferation in rat MC was examined with MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide).IL-6 messenger ribonucleic acid(mRNA),TGF-β1mRNA and Smad7mRNA were also examined with reverse transcription-polymerase chain reaction(RT-PCR).Results 1.In YSTL groups,the 24huPro,Scr and BUN decreased, while Alb increased.Also,in YSTL groups,the pathological damage, positive area ratio,the deposition of IL-6 and TGF-β1 decreased and Smad7 increased in kidney.They(especially the middle-dosage and high-dosage group) were much better than either the pathological pattern group or SYSW one respectively(P<0.05,P<0.01).2.There was a positive linear correlation between IL-6 and TGF-β1(P<0.01),but a negative one between Smad7 and either IL-6 or TGF-β1(P<0.05,P<0.01).3.The serum of YSTL,especially the high-dosage one,restrained the proliferation in rat MC better(P<0.05,P<0.01).The expression of Smad7mRNA was promoted in high-dosage serum group,but IL-6mRNA and TGF-β1mRNA were descended(P<0.01).Conclusion 1.YSTL had obvious effects on rats with nephrotic syndrome(NS).It could improve the relative proteins and the functions of kidney,and reduce the pathological damages.One of its mechanism might be restraining the proliferation in rat MC.2.YSTL could restrain the proliferation in rat MC effectively.One of its molecular mechanism was adjusting the relations among Smad7/TGF-β1/IL-6.3.The basic pathogenesis of NS is deficiency of the kidney accompanied with blood-stasis.The main methods of treatment is reinforcing the kidney and eliminating the stasis.4.YSTL is an effective pharmaceutical.