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基于肠道菌群探究清瘟败毒饮对脓毒症肾损伤大鼠的治疗作用及机制
王翠菡,杨磊,武玉琳,王俊锋,徐桐柏
0
天津市中西医结合医院·天津市南开医院天津 300100;天津中医药大学南开临床学院天津 300100;天津市急腹症器官损伤与中西医修复重点实验室天津 300100;天津市中西医结合急腹症研究所天津 300100;天津医科大学肿瘤医院,国家恶性肿瘤临床医学研究中心天津 300060;天津市恶性肿瘤临床医学研究中心天津 300060;天津市肿瘤防治重点实验室天津 300060
摘要:
目的:研究清瘟败毒饮(QWBD)对脓毒症肾损伤大鼠的治疗作用及机制。方法:取50只健康雄性SD大鼠,根据随机数字表法分为对照组,模型组,QWBD低、中、高剂量组,生化检测大鼠血清中感染指标(白细胞计数、C反应蛋白、降钙素原、血清淀粉样蛋白A等)和肝肾功能指标(血肌酐、尿素氮、谷丙转氨酶、谷草转氨酶);HE观察肾组织病理学改变;免疫组化检测大鼠肾组织中髓过氧化物酶(MPO)、瓜氨酸组蛋白H3(Cit-H3);16SrDNA测序检测肠道菌群变化情况。结果:与模型组相比,QWBD各剂量组均能一定程度降低大鼠感染指标,能一定程度改善大鼠受损的肝肾功能;大鼠肾组织HE染色结果发现,模型组大鼠肾脏组织结构严重破坏,QWBD各剂量组肾小囊扩张逐渐减少,肾小管上皮细胞水样变性逐渐减少,肾小管上皮细胞逐渐圆润、饱满;与模型组相比,QWBD各剂量组大鼠肾组织中MPO、Cit-H3蛋白的阳性率均明显降低(P <0.01);各组大鼠肠道菌群分析结果显示,在alpha多样性上,QWBD各剂量组均能升高Chao1、Simpson、Shannon指数;beta多样性显示,模型组与对照组对比肠道菌落存在差异,QWBD各组与模型组、对照组对比均存在差异,beta多样性较高;物种组成热图分析提示QWBD干预后有益菌增多、有害菌减少,在门、纲、目、科、属各水平提示模型组有害菌明显较多,QWBD组有益菌明显较多,提示QWBD能够显著改善肠道菌群。结论:QWBD对脓毒症肾损伤大鼠的治疗作用明确,其治疗机制可能与通过调节肠道菌群,抑制中性粒细胞胞外诱捕网相关。
关键词:  脓毒症肾损伤  清瘟败毒饮  肠道菌群  中性粒细胞胞外诱捕网
DOI:10.3969/j.issn.1007-6948.2026.01.024
投稿时间:2025-05-14
基金项目:天津市卫健委中西医结合课题(2023171、2023157);河北省中医药科研项目(T2025061);天津医科大学学科提升计划中西医结合专项(2024XKZXY17);天津市医学重点学科建设资助(TJYXZDXK-3-028C);天津市教委科研计划项目(2025KJ074)
Exploring the therapeutic effect and mechanism of Qingwen Badu decoction on sepsis-induced renal injury based on gut microbiota
WANG Cui-han,YANG Lei,WU Yu-lin
Abstract:
Objective: To investigate the therapeutic effect and mechanism of Qingwen Baidu(QWBD) decoction on septic kidney injury rats. Methods Fifty healthy male SD rats were randomly divided into five groups: Sham group, CLP group, QWBD low, medium, and high dose groups according to a random number table. Biochemical tests were conducted to detect infection indicators and liver and kidney function in the serum of the rats; HE observation of pathological changes in renal tissue; Immunohistochemical detection of MPO and Cit-H3 in rat kidney tissue; 16SrDNA sequencing was used to detect changes in gut microbiota. Results Compared with the CLP group, all dose groups of QWBD were able to reduce the infection index of rats to a certain extent and improve the damaged liver and kidney function of rats to a certain extent; The HE staining results of rat kidney tissue showed that the structure of the kidney tissue in the CLP group was severely damaged, and the dilation of renal small sacs gradually decreased in each dose group of QWBD. The watery degeneration of renal tubular epithelial cells gradually decreased, and the renal tubular epithelial cells gradually became round and full; Compared with CLP, the positive expression of MPO and Cit-H3 proteins in the renal tissue of rats in each dose group of QWBD was significantly reduced (P <0.01); The analysis of gut microbiota in each group of rats showed that in terms of alpha diversity, all dose groups of QWBD were able to increase Chao1, Simpson, and Shannon indices; In the beta diversity display, there were differences in gut microbiota between the CLP group and the Sham group, as well as differences between the QWBD group and both the CLP and Sham groups. The beta diversity was relatively high; Species composition heatmap analysis suggests an increase in beneficial bacteria and a decrease in harmful bacteria after QWBD intervention. At the phylum, class, order, family, and genus levels, it suggests that the CLP group has significantly more harmful bacteria, while the QWBD group has significantly more beneficial bacteria, indicating that QWBD can significantly improve gut microbiota. Conclusion QWBD has a clear therapeutic effect on septic kidney injury rats, and its therapeutic mechanism may be related to regulating gut microbiota and inhibiting NETs.
Key words:  Sepsis-induced kidney injury  Qingwen Badu decoction  gut microbiota NETs

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