首页|基于JAK/STAT3通路探讨补肾活血方改善单侧输尿管梗阻大鼠炎症和肾纤维化

基于JAK/STAT3通路探讨补肾活血方改善单侧输尿管梗阻大鼠炎症和肾纤维化

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目的:观察补肾活血方(BSHXF)对单侧输尿管梗阻大鼠(unilateral ureteral obstruction,UUO)肾纤维化和炎症的治疗效果,揭示其抗炎及延缓肾纤维化的机制.方法:32 只8 周龄雌性SD大鼠根据随机数字表分为假手术组(Sham组)、单侧输尿管梗阻组(UUO组)、补肾活血方低剂量组(BSHXF-L组)和补肾活血方高剂量组(BSHXF-H组).造模后第2 天开始,连续灌胃干预21 d,BSHXF-L组和BSHXF-H组给予相应剂量补肾活血方汤剂,Sham组和UUO组给予与BSHXF组等体积的生理盐水.干预结束后,记录24h尿量,全自动生化分析仪检测血肌酐、尿素氮、尿蛋白、尿肌酐和肾功能指数;采用HE和Masson染色检测肾脏病理损伤和纤维化程度;通过免疫组化染色分析各组TGF-β和TNF-α;Western blotting 检测各组TGF-β1、α-SMA、JAK、STAT3、p-STAT3、TNF-α、Caspase-3 和Bax的蛋白表达情况.结果:与UUO模型组相比,BSHXF-L组和BSHXF-H组能明显明显改善UUO大鼠的肾功能,降低大鼠肾组织中TGF-β1 和α-SMA蛋白表达水平,抑制JAK、STAT3 和p-STAT3 表达,减少炎症细胞浸润和纤维组织以及胶原的增生,显著降低大鼠的肾脏指数和TNF-α等炎症指标.结论:补肾活血方可通过抑制JAK/STAT3 通路激活,改善UUO大鼠肾功能,减轻其肾脏炎症水平、肾脏指数,延缓肾纤维化进程.
Bushen Huoxue Formula Alleviated Inflammation and Renal Fibrosis in a Unilateral Ureteral Obstruction Rat Model by Inhibiting JAK/Stat3 Pathway
Objective:This study is to observe the therapeutic effect of Bushen Huoxue Formula(BSHXF)on Inflammation and Renal Fibrosis in rats with Unilateral ureteral obstruction(UUO),thus revealing the mechanism of its anti-renal fibrosis and in-flammation.Methods:32 8-week-old female SD rats were randomly divided into Sham group(sham surgery group),UUO group(unilateral ureteral obstruction group),BSHXF-L group(low-dose group of BSHXF),and BSHXF-H group(high-dose group of BSHXF)based on a random number table.Continuous gastric lavage intervention was performed for 21 days from the second day af-ter modeling.The BSHXF-L and BSHXF-H groups were given corresponding doses of BSHXF,while the Sham and UUO groups were given physiological saline of the same volume as the BSHXF group.Results:After the intervention,24-hour urine output was recorded;a fully automated biochemical analyzer was used to detect blood creatinine,urea nitrogen,urinary protein,urinary creati-nine,and renal function index;HE and Masson staining were used to detect the degree of pathological damage and fibrosis;Analysis of TGF-β and TNF-α in each group by immunohistochemistry staining;Western blotting detection of TGF-β1、α-SMA、JAK、STAT3、p-STAT3、TNF-α、The protein expression of Caspase-3 and Bax in each group.Conclusion:Compared with the UUO group,the BSHXF-L and BSHXF-H groups significantly improve renal function of SD with UUO,reduced the expression level of TGF-β1 and α-SMA protein in rat kidney tissue and inhibited the expression of JAK,STAT3,and p-STAT3,reduced the infiltra-tion of inflammatory cells and the proliferation of fibrous tissue and collagen,significantly reduced the renal index of rats,and the oth-er inflammatory indicators of TNF-α et al in rats'kidneys.Conclusion:BSHXF can effectively improve renal function,alleviate in-flammation and renal fibrosis in rats with unilateral ureteral ligation by inhibiting of JAK/STAT3 pathway signaling.

Bushen huoxue formulaRenal fibrosisJAK/STAT3A rat model of unilateral ureteral obstruction

廖琳、徐启明、陶鹏宇、胡静、陈杰、张传富、刘文瑞、路建饶

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上海中医药大学附属第七人民医院 (上海 200137)

补肾活血方 肾纤维化 JAK/STAT3 单侧输尿管梗阻大鼠模型

国家自然科学基金上海市第七人民医院"北斗星"人才培养计划

82074261BDX2023-01

2024

中国中西医结合肾病杂志
中国中西医结合学会

中国中西医结合肾病杂志

CSTPCD
影响因子:1.061
ISSN:1009-587X
年,卷(期):2024.25(3)
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