| ObjectiveTo investigate the effect of sinomenine on heme oxygenase-1(HO-1), and explore the suggestive molecular mechanisms of SIN in protecting the rats with chronic nephrotoxicity by cyclosporine A, it will provide the experimental and theoretical basis on clinical application.MethodsSelect 64 healthy male SD rats, CsA-pouring stomach to establish the model of chronic renal toxicity using classic sodium depletion method, which was built by Rosen. the rats were randomly divided into four groups: (1)low-salt group(the control group), (2)SIN group, (3)CsA group, (4)SIN+CsA group. Observed the change of weight, after 14,28 days took the urine to measured the urine of 24 hours, took the blood to measure the serum creatinine and blood urea nitrogen values. The rats were killed after 28 days, tooke the blood from IVC to measure the serum creatinine and blood urea nitrogen values. Got the kidney tissue to make the biopsy,immunohistochemistry and RT-PCR to observe the pathologiccal changes of kidney, as well as the expression of HO-1.Results(1) Compared with the controlled group, the body weight of CsA group significantly decreased (P <0.05), the urinary volume of 24 hours, CR and BUN significantly increased(P <0.05). Compared with the CsA group, SIN+CsA group the body weight of CsA group significantly increased (P <0.05), the urinary volume of 24 hours, CR and BUN significantly decreased(P <0.05).(2) Compared with the controlled group,in renal pathological changes,CsA group had the proximal tubule epithelial cell swelling, even degeneration and dissolution and necrosis. Interstitial inflammatory cells scattered or focal infiltration, mild fibrosis. SIN+CsA group and CsA group more better than controlled group.(3) Compared with the controlled group, the expression of HO-1 was decreased obviously(P <0.05)in immunohisto chemistry technique and RT-PCR. Compared with the CsA group, the expression of HO-1 was increased obviously(P <0.05)in immunohisto chemistry technique and RT-PCR.ConclusionCsA-pouring stomach can establish the model of chronic nephrotoxicity in rats. CsA reduce the expression of HO-1, while combine with sinomenine, the expression of HO-1 up-regulation. SIN has some protective effect on the chronic CsA nephrotoxicity, this mechanism may be play a role through up-regulating the expression of HO-1. |
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