首页|黑地黄丸通过调控IGF-1表达对慢性肾衰竭大鼠肾纤维化的抑制作用

黑地黄丸通过调控IGF-1表达对慢性肾衰竭大鼠肾纤维化的抑制作用

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目的 探讨黑地黄丸对慢性肾衰竭大鼠肾纤维化的影响及其作用机制.方法 Wistar大鼠随机分为空白组(正常饲养)和造模组,造模组大鼠采用 5/6 肾切除手术构建CRF大鼠模型.将造模成功的大鼠随机分为模型组、黑地黄丸组(10.43 g/kg)及黑地黄丸+IGF-1R阻断剂(JB1)组(连续7d皮下注射18 μg/kg JB1 后灌胃10.43 g/kg黑地黄丸).给药 8 周后,检测大鼠血清Scr、BUN水平,HE和Masson染色观察肾组织病理变化,免疫组化法检测肾组织TGF-β、HIF-1α、α-SMA蛋白表达,Western blot 法检测肾组织 IGF-1R、TGF-β 蛋白表达,RT-qPCR 法检测肾组织IGF-1R、TGF-β mRNA表达.结果 与空白组比较,模型组血清Scr、BUN水平升高(P<0.05),肾组织纤维化程度加重,纤维化面积增加(P<0.05),肾组织TGF-β、HIF-1α、α-SMA蛋白表达和TGF-β mRNA表达升高(P<0.05),IGF-1R mRNA和蛋白表达降低(P<0.05);与模型组比较,黑地黄丸组大鼠血清Scr、BUN水平降低(P<0.05),肾间质炎性细胞减少,纤维化程度减轻(P<0.05),肾组织TGF-β、HIF-1α、α-SMA蛋白表达和TGF-β mRNA表达降低(P<0.05),IGF-1R mRNA和蛋白表达升高(P<0.05);而给予JB1 可减弱黑地黄丸对CRF大鼠肾纤维化的改善作用(P<0.05).结论 黑地黄丸能够抑制CRF大鼠肾纤维化,且该抑制过程与上调IGF-1 表达,促进IGF-1 与IGF-1R结合有关.
Inhibitory effect of Heidihuang Pills on renal fibrosis in a rat model of chronic renal failure via regulation of IGF-1 expression
AIM To explore the effect of Heidihuang Pills on renal fibrosis in a rat model of chronic renal failure(CRF)and its mechanism.METHODS Wistar rats were randomly divided into the blank group for normal feeding and the model group for the establishment of CRF rat models by 5/6 nephrectomy.Subsequently,the successfully established rat models were randomly divided into the model group,the Heidihuang Pills group(10.43 g/kg),and the Heidihuang Pills+IGF-1R blocker(JB1)group for a regimen of 7-day subcutaneous injection of 18 μg/kg JB1 followed by gavage of 10.43 g/kg Heidihuang Pills.Eight weeks after the administration,the rats had their serum levels of Scr and BUN detected;their pathological changes of renal tissue observed by HE and Masson staining;their renal protein expressions of TGF-β,HIF-1α and α-SMA detected by immunohistochemistry;their renal protein expressions of IGF-1R and TGF-β detected by Western blot;and their renal mRNA expressions of IGF-1R and TGF-β detected by RT-qPCR.RESULTS Compared with the blank group,the model group displayed increased serum levels of Scr and BUN(P<0.05);increased,degree of renal fibrosis,and renal fibrosis area(P<0.05);increased renal expressions of TGF-β,HIF-1α,α-SMA proteins and TGF-β mRNA(P<0.05);and decreased expressions of IGF-1R mRNA and protein(P<0.05).Compared with the model group,the Heidihuang Pills group displayed decreased serum Scr and BUN levels(P<0.05);decreased inflammatory cells in renal interstitium and the fibrosis degree(P<0.05);decreased renal expressions of TGF-β,HIF-1α,α-SMA proteins and TGF-β mRNA(P<0.05);and increased expressions of IGF-1R mRNA and protein(P<0.05).However,the administration of JB1 could weaken the improvement effect of Heidihuang Pills on renal fibrosis in CRF rats(P<0.05).CONCLUSION Heidihuang Pills can inhibit the renal fibrosis in CRF rats,and the inhibition process is related to up-regulated IGF-1 expression and promoted combination of IGF-1 and IGF-1R.

Heidihuang Pillschronic renal failurerenal fibrosisinsulin-like growth factor

叶莉莹、潘广辉、赵平、王泽鹏、柳成、李颖颖、张法荣

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山东中医药大学,山东 济南 250355

山东中医药大学附属医院,山东 济南 250012

泰安市中医院,山东 泰安 271000

北大医疗淄博医院,山东 淄博 255000

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黑地黄丸 慢性肾衰竭 肾纤维化 胰岛素样生长因子

国家自然科学基金面上项目

81774251

2024

中成药
国家食品药品监督管理局,信息中心中成药信息站,上海中药行业协会

中成药

CSTPCD北大核心
影响因子:1.217
ISSN:1001-1528
年,卷(期):2024.46(3)
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