| 王霞,孙东云,王香婷,王筝,王聪慧,许庆友.柴苓汤对慢性环孢素A肾损伤的防护作用及其机制研究[J].中国中西医结合杂志,2012,32(8):1083-1087 |
| 柴苓汤对慢性环孢素A肾损伤的防护作用及其机制研究 |
| Protective Effects of Chailing Decoction on Cyclosporine A Induced Chronic Renal Injury and Its Mechanisms |
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| DOI： |
| 中文关键词: 柴苓汤 慢性环孢素A肾病 转化生长因子-β1 结缔组织生长因子 细胞凋亡 细胞增殖 |
| 英文关键词:Chailing Decoction chronic cyclosporine A nephropathy transforming growth factor-β1 connective tissue growth factor cell apoptosis cell proliferation |
| 基金项目:河北省优秀专家出国培训资助项目(No.200892) |
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| 中文摘要: |
| 目的观察柴苓汤对慢性环孢素A肾病(chronic cyclosporine A nephropathy,CCN)大鼠肾脏转化生长因子-β1(transforming growth factor-β1,TGF-β1)、结缔组织生长因子(connective tissue growth factor,CTGF)表达及细胞凋亡、增殖的影响,探讨其拮抗肾纤维化的可能作用机制。方法采用经口灌服环孢素A[cyclosporineA,CsA,30mg/(kg·d)]的方法复制慢性环孢素A肾病大鼠模型,同时灌胃给予中药柴苓汤[3g/(kg·d)]治疗。测定大鼠肾功能指标血清尿素氮(BUN)、血清肌酐(SCr)及肌酐清除率(CCr);Masson染色观察肾小管间质纤维化程度;免疫组化、RT-PCR观察TGF-β1、CTGF蛋白及基因表达;流式细胞术检测肾脏细胞凋亡率、增殖指数。结果与对照组[BUN(mmol/L):6.123±0.588;SCr(μmol/L):75.654±8.196;CCr(mL/min):0.539±0.169]比较,模型组大鼠肾功能(BUN:11.600±1.437;SCr:101.985±10.809;CCr:0.272±0.060)明显降低(P<0.01);肾间质区胶原成分明显增多;肾小管上皮细胞及间质细胞TGF-β1、CTGF蛋白及mRNA表达显著增强(P<0.01);肾脏细胞增殖指数及凋亡率均有所上升,但凋亡/增殖的比值(0.317±0.059)较对照组(0.680±0.150)下降(P<0.01)。经中药柴苓汤治疗,大鼠肾功能(BUN:7.340±0.857;SCr:84.923±10.627;CCr:0.405±0.081)显著提高(P<0.05,P<0.01),间质区胶原成分沉积减少;TGF-β1、CTGF蛋白及mRNA高表达下调(P<0.01),肾脏细胞凋亡/增殖的比值(0.650±0.092)提高(P<0.01)。结论柴苓汤能够改善CCN模型大鼠肾功能,抑制TGF-β1、CTGF表达,并通过诱导细胞凋亡,抑制细胞增殖,恢复细胞凋亡与增殖的平衡,从而延缓肾间质纤维化进程。 |
| 英文摘要: |
| Objective To observe the effects of Chailing Decoction(CD) on transforming growth factor-β1(TGF-β1),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.Methods The CCN rat model was prepared using oral administration of cyclosporine A(CsA,30 mg·kg-1·d-1).Meanwhile,they were treated with CD(3 g·kg-1·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-β1 and CTGF were observed using immunohistochemical assay and RT-PCR.The renal cell apoptosis rate and the proliferation index were detected by flow cytometry.Results Compared with the control group(BUN:6.123±0.588 mmol/L;SCr:75.654±8.196 μmol/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 μmol/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-β1 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-β1 and CTGF were down-regulated(P<0.01),the ratio of apoptosis to proliferation increased(0.650±0.092,P<0.01).Conclusion CD could improve the renal function of CCN model rats,inhibit the expressions of TGF-β1 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. |
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