Protective effects of chailing decoction on cyclosporine A induced chronic renal injury and its mechanisms / 中国中西医结合杂志

ABSTRACT

<p><b>OBJECTIVE</b>To observe the effects of Chailing Decoction (CD) on transforming growth factor-beta1 (TGF-beta1), connective tissue growth factor (CTGF), renal cell apoptosis and proliferation in rats with chronic cyclosporine A nephropathy (CCN), and to explore its possible mechanism for inhibiting renal fibrosis.</p><p><b>METHODS</b>The CCN rat model was prepared using oral administration of cyclosporine A (CsA, 30 mg x kg(-1) x d(-1)). Meanwhile, they were treated with CD (3 g x kg(-1) x d(-1)) by gastrogavage. The serum blood urea nitrogen (BUN), serum creatinine (SCr), and creatinine clearance rate (CCr) were measured by the end of the fourth week of the experiment. The kidneys were taken out on the next day. The degree of renal fibrosis was detected using Masson staining. The protein and gene expressions of TGF-beta1, and CTGF were observed using immunohistochemical assay and RT-PCR. The renal cell apoptosis rate and the proliferation index were detected by flow cytometry.</p><p><b>RESULTS</b>Compared with the control group (BUN 6.123 +/- 0.588 mmol/L; SCr 75.654 +/- 8.196 micromol/L; CCr 0.539 +/- 0.169 mL/min), the renal function of the model group (BUN 11.600 +/- 1.437 mmol/L; SCr 101.985 +/- 10.809 micromol/L; CCr 0.272 +/- 0.060 mL/min) obviously declined (P < 0.01). The collagen deposition in the renal interstitial area significantly increased. The protein and mRNA expressions of TGF-beta1, and CTGF in the tubular epithelial cells and the mesenchymal cells were significantly enhanced (P < 0.01). The cell proliferation index and the apoptosis rate both increased, but the ratio of apoptosis to proliferation (0.317 +/- 0.059) decreased more than that in the control group (0.680 +/- 0.150, P < 0.01). After treatment by CD, the renal function (BUN 7.340 +/- 0.857; SCr 84.923 +/- 10.627; CCr 0.405 +/- 0.081) was significantly enhanced (P < 0.05, P < 0.01), the collagen deposition decreased, the high protein and mRNA expressions of TGF-beta1 and CTGF were down-regulated (P < 0.01), the ratio of apoptosis to proliferation increased (0.650 +/- 0.092, P<0. 01).</p><p><b>CONCLUSION</b>CD could improve the renal function of CCN model rats, inhibit the expressions of TGF-beta1 and CTGF, and recover the balance between the renal cell apoptosis and proliferation by inducing cell apoptosis and inhibiting cell proliferation, thus delaying the renal fibrosis process.</p>