二至丸对脓毒症急性肾损伤的保护作用及机制  

Protective effect and mechanism of Erzhi Pills on sepsis associated acute kidney injury

作　　者：何爱凤 蔡志慧 肖建鹏 蒋俊[3] 尹江宁 陈义坤[5] HE Ai-feng;CAI Zhi-hui;XIAO Jian-peng;JIANG Jun;YIN Jiang-ning;CHEN Yi-kun(Medical College of Jiangsu University,Zhenjiang 212013,China;Yancheng Binhai County People’s Hospital,Yancheng 224000,China;School of Pharmacy,Jiangsu University,Zhenjiang 212013,China;The Affiliated Jiangning Hospital of Nanjing Medical University,Nanjing 211100,China;Affiliated Hospital of Jiangsu University,Zhenjiang 212013,China)

机构地区：[1]江苏大学医学院,镇江212013 [2]盐城市滨海县人民医院,盐城224000 [3]江苏大学药学院,镇江212013 [4]南京医科大学附属江宁医院急诊科,南京211100 [5]江苏大学附属医院,镇江212013

出　　处：《中华中医药杂志》2022年第8期4309-4314,共6页China Journal of Traditional Chinese Medicine and Pharmacy

基　　金：国家自然科学基金项目(No.81703773);江苏省自然科学基金项目(No.BK20170560);江苏省中医药科技发展计划(No.MS2021104);徐州医科大学江苏省重点实验室开放课题(No.XZSYSKF2021043)。

摘　　要：目的:观察二至丸改善脓毒症急性肾损伤(SA-AKI)的药效作用,并探讨其多通路作用机制。方法:选取SD大鼠24只,分为空白组、假手术组、模型组、二至丸组,每组6只,二至丸组于术前灌胃给药二至丸(3.78g/kg,1次/d),连续3d,其他组灌以同体积的蒸馏水,于第4天对模型组及二至丸组采用盲肠结扎穿孔造模,假手术组打开腹腔后直接缝合。各组于给药前、造模前及造模后的6、12、24h,采用酶联免疫吸附测定法检测血清中血肌酐、血尿素氮及炎症因子,RT-PCR法和蛋白免疫印迹法检测肾组织中相关基因和蛋白的表达量,采用HE染色观察肾小管、肾小球形态学改变。结果:与空白组比较,模型组在造模型后6、12、24h血肌酐、血尿素氮、肿瘤坏死因子(TNF)-α、白细胞介素(IL)-6、IL-4、IL-10水平均显著升高(P<0.05),肾组织中TNF-αmRNA表达水平显著上调(P<0.05),肾组织中TNF-α、NF-κBp-p65、p-p38MAPK蛋白相对含量显著升高(P<0.05);与模型组比较,二至丸组在造模后6、12、24h血清中血肌酐、血尿素氮、TNF-α、IL-6水平显著降低(P<0.05),血清中IL-4、IL-10水平均显著升高(P<0.05),肾组织中TNF-αmRNA表达水平显著下调(P<0.05),肾组织中TNF-α、NF-κBp-p65、p-p38 MAPK蛋白相对含量显著降低(P<0.05)。HE染色结果表明,二至丸干预后的SA-AKI大鼠肾小管、肾小球病理形态完整,肾间质间轻度水肿、炎性细胞少量浸润,较模型组明显改善。结论:推测二至丸可通过抑制TNF-α/NF-κB、p38 MAPK多信号通路的磷酸化进而抑制炎症因子的释放,发挥预防SA-AKI的作用。Objective:To observe the pharmacodynamic effects of Erzhi Pills on sepsis associated acute kidney injury(SA-AKI),and to explore its multi-pathway mechanism.Methods:Twenty-four SD rats were selected and divided into blank group,sham operation group,model group and Erzhi Pills group,6 rats in each group.The Erzhi Pills group were given Erzhi Pills(3.78 g/kg,once a day)by intragastric administration before operation for three consecutive days.The other groups were given the same volume of distilled water,and the model group and Erzhi Pills group were given cecal ligation perforation on the fourth day.In the sham operation group,the abdominal cavity was opened and sutured directly.Before treatment,modeling and at 6 h,12 h and 24 h after modeling,serum creatinine,blood urea nitrogen and inflammatory factors in each group were detected by enzyme-linked immunosorbent assay.Then,the expression levels of related genes and proteins in kidney tissues were detected by RT-PCR and Western blot.Morphological changes of renal tubules and glomerulus were observed by HE staining.Results:Compared with blank group,serum creatinine,blood urea nitrogen,TNF-α,IL-6,IL-4 and IL-10 levels in model group were significantly increased at 6 h,12 h and 24 h postoperatively(P<0.05),TNF-αmRNA expression in renal tissue was significantly up-regulated(P<0.05),the relative contents of TNF-α,NF-κBp-p65 and p-p38 MAPK protein in renal tissue were significantly increased(P<0.05);Compared with model group,the levels of serum creatinine,blood urea nitrogen,TNF-αand IL-6 in Erzhi Pills group were significantly decreased at 6 h,12 h and 24 h(P<0.05),serum IL-4 and IL-10 levels were significantly increased(P<0.05),TNF-αmRNA expression in renal tissue was significantly down-regulated(P<0.05),the relative contents of TNF-α,NF-κBp-p65 and p-p38 MAPK protein in renal tissue were significantly decreased(P<0.05);HE staining results showed that the pathological morphology of renal tubules and glomerulus in the SA-AKI rats after Erzhi Pills intervention wa

关 键 词：脓毒症急性肾损伤 二至丸 TNF-α/NF-κB信号通路 P38-MAPK信号通路 炎症因子 

分 类 号：R285.5[医药卫生—中药学]