夏芳, 万亚琴, 胡龙, 夏倩, 王愿达, 刘金霞. 青蒿琥酯通过白细胞介素6/转录激活因子3信号通路对紫癜性肾炎大鼠肾脏保护作用机制研究[J]. 临床肾脏病杂志, 2022, 22(12): 1030-1035. DOI: 10.3969/j.issn.1671-2390.2022.12.010
    引用本文: 夏芳, 万亚琴, 胡龙, 夏倩, 王愿达, 刘金霞. 青蒿琥酯通过白细胞介素6/转录激活因子3信号通路对紫癜性肾炎大鼠肾脏保护作用机制研究[J]. 临床肾脏病杂志, 2022, 22(12): 1030-1035. DOI: 10.3969/j.issn.1671-2390.2022.12.010
    Xia Fang, Wan Ya-qin, Hu Long, Xia Qian, Wang Yuan-da, Liu Jin-xia. Protective effect mechanism of artesunate on rat kidney with purpuric nephritis through IL-6/ STAT3 signaling pathway[J]. Journal of Clinical Nephrology, 2022, 22(12): 1030-1035. DOI: 10.3969/j.issn.1671-2390.2022.12.010
    Citation: Xia Fang, Wan Ya-qin, Hu Long, Xia Qian, Wang Yuan-da, Liu Jin-xia. Protective effect mechanism of artesunate on rat kidney with purpuric nephritis through IL-6/ STAT3 signaling pathway[J]. Journal of Clinical Nephrology, 2022, 22(12): 1030-1035. DOI: 10.3969/j.issn.1671-2390.2022.12.010

    青蒿琥酯通过白细胞介素6/转录激活因子3信号通路对紫癜性肾炎大鼠肾脏保护作用机制研究

    Protective effect mechanism of artesunate on rat kidney with purpuric nephritis through IL-6/ STAT3 signaling pathway

    • 摘要: 目的 探究青蒿琥酯通过白细胞介素(interleukin, IL)6/信号转导和转录激活因子3(signal transducer and activator of transcription 3,STAT3)信号通路对紫癜性肾炎(henoch schonlein purpura nephritis,HSPN)大鼠肾脏保护作用机制。方法 建立HSPN大鼠模型,采用随机数字表法随机分为模型组、青蒿琥酯低剂量组(15mg/kg)组、青蒿琥酯高剂量(30mg/kg)组、青蒿琥酯(30mg/kg)+colivelin(IL-6/STAT3信号激活剂,1mg/kg)组,每组12只模型大鼠,另选12只SD大鼠作为对照组,分组处理大鼠后,检测各组大鼠肾功能指标、肾组织病理形态、肾脏免疫球蛋白(immunoglobulin, Ig)A沉积、血清IgA及循环免疫复合物(circulation immune complex,CIC)、IL-18、IL-6水平、肾组织IL-6/STAT3通路相关蛋白表达。结果 与对照组相比,模型组大鼠肾脏组织产生严重病理损伤为:肾小球系膜和基底膜增生明显,肾小球硬化,肾小管肿胀,且肾脏组织中有大量炎症细胞浸润,血肌酐(serum creatinine,Scr)和血尿素氮(blood urea nitrogen, BUN)水平、24h尿蛋白定量、血清IgA、CIC、IL-18及IL-6水平、肾组织IgA平均荧光强度、p-STAT3/STAT3及IL-6蛋白表达水平显著升高(P<0.05);与模型组相比,青蒿琥酯低、高剂量组大鼠肾脏组织病理损伤均减轻,Scr和BUN水平、24h尿蛋白定量、血清IgA、CIC、IL-18及IL-6水平、肾组织IgA平均荧光强度、p-STAT3/STAT3及IL-6蛋白表达水平均降低(P<0.05),且高剂量青蒿琥酯作用更强;与青蒿琥酯高剂量组相比,青蒿琥酯+colivelin组大鼠肾脏组织病理损伤加重,Scr和BUN水平、24h尿蛋白定量、血清IgA、CIC、IL-18及IL-6水平、肾组织IgA平均荧光强度、pSTAT3/STAT3及IL-6蛋白表达水平升高(P<0.05)。结论 青蒿琥酯通过抑制IL-6/STAT3信号激活而减轻炎症,减少肾脏IgA沉积,缓解HSPN大鼠肾损伤,发挥肾脏保护作用。

       

      Abstract: Objective To explore the protective effect mechanism of artesunate on rat kidney with Henoch Schonlein purpuric nephritis(HSPN)through the signaling pathway of interleukin(IL)-6/ signal transducer and activator of transcription 3(STAT3). Methods After an induction of HSPN, Sprague-Dawley(SD)rats were randomized into four groups of model with random number table methods,low-dose artesunate(15 mg/kg),high-dose artesunate(30 mg/kg)and artesunate(30 mg/kg) plus colivelin(IL-6/STAT3 signaling activator,1 mg/kg)(n=12 each). Another 12 SD rats were selected as control group. Renal function parameters,pathological morphology of renal tissue,deposition of IgA,serum levels of immunoglobulin A(IgA),circulating immune complex(CIC),IL-18 and IL-6 and the expressions of IL-6/STAT3 pathway-related proteins in renal tissue were recorded. Results As compared with control group,renal tissue of rats in model group manifested severe pathological injuries of obvious hyperplasia of mesangium and basement membrane of glomerulus,glomerular sclerosis,swelling of renal tubules,and a large number of inflammatory cells infiltration,serum levels of(creatinine, Cr),(blood urea nitrogen,BUN),24-hour urine protein,IgA,CIC,IL-18 and IL-6,renal tissue IgA mean fluorescent intensity,protein expression levels of p-STAT3/STAT3 and IL-6 spiked markedly(P<0. 05);as compared with model group,pathological injury of renal tissue lessoned in low/high-dose artesunate group. serum levels of Cr,BUN,24-hour urine protein,IgA,CIC,IL-18 and IL-6,renal tissue IgA mean fluorescent intensity,protein expression levels of p-STAT3/STAT3 and IL-6 declined(P<0. 05);high-dose artesunate had more potent effect;as compared with high-dose artesunate group,renal tissue pathological injury worsened in artesunate+colivelin group. Serum levels of Cr and BUN,24-hour urine protein,IgA,CIC,IL-18 and IL-6,renal tissue IgA mean fluorescent intensity and protein expression levels of p-STAT3/STAT3 and IL-6 increased(P<0. 05). Conclusion Through suppressing the activation of IL-6/STAT3 signaling,artesunate may reduce inflammation,lower the deposition of IgA,alleviate renal injury and exert renal protection in HSPN rats.

       

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