炎调方调控HMGB1通路对脓毒症急性肺损伤大鼠线粒体功能的保护作用研究  

Protective Effect of Yantiao Decoction Regulation of HMGB1 Pathway on Mitochondrial Function in Rats with Acute Lung Injury Induced by Sepsis

作　　者：吕弈宾 陈乾[1] 熊旭东[1] 谢芳[1] 李淑芳[1] LüYibing;Chen Qian;Xiong Xudong;Xie Fang;Li Shufang(Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine,Shanghai 201209,China)

机构地区：[1]上海中医药大学附属曙光医院,上海201203

出　　处：《中国中医急症》2020年第11期1897-1901,共5页Journal of Emergency in Traditional Chinese Medicine

基　　金：国家自然科学基金面上项目(81974539);上海中医药大学预算内项目(2019LK020)。

摘　　要：目的观察炎调方对脓毒症急性肺损伤(ALI)大鼠高迁移率族蛋白1(HMGB1)和线粒体功能的影响,探讨其治疗脓毒症ALI的作用机制。方法40只SD雄性大鼠随机分为假手术组、模型组、炎调方组和乌司他丁组,每组10只。各给药组给予相应药物灌胃或腹腔注射,灌胃每日1次,连续3 d,腹腔注射于盲肠结扎穿孔后实施。末次灌胃后2 h采用盲肠结扎穿孔术造模,于术后24 h处死大鼠,观察大鼠一般情况,肺组织HE染色,电镜观察肺组织线粒体超微结构,分光光度计检测肺组织线粒体Na^+-K^+-ATP酶和Ca^2+-Mg^2+-ATP酶,PCR检测HMGB1 m RNA水平表达情况。结果与假手术组相比,模型组可见肺组织结构明显破坏,线粒体数量明显减少,体积变小,嵴断裂脱落甚至出现空泡化,内外膜出现破损,Na^+-K^+-ATP酶、Ca^2+-Mg^2+-ATP酶和超氧化物歧化酶(SOD)活性明显下降(P<0.01),丙二醛(MDA)含量和HMGB1 mRNA表达水平明显上升(P<0.01)。与模型组相比,炎调方组肺组织及线粒体超微结构损伤程度减轻,Na^+-K^+-ATP酶、SOD活性回升(P<0.01),MDA含量和HMGB1 m RNA的表达水平明显下降(P<0.05)。结论炎调方能通过下调HMGB1水平,防止线粒体进一步损伤,从而达到减轻脓毒症ALI大鼠肺组织损伤的作用。Objective:To observe the effect of Yantiao Decoction(YTD)on HMGB1 and mitochondrial function in rats with acute lung injury(ALI)induced by sepsis,and to observe the mechanism of YTD in ALI.Methods:A total of 40 SD male rats were randomly divided into the sham group,CLP group,YTD group,and ulinastatin(WSTD)group,10 rats in each group.Each drug group was given corresponding drugs by gavage or intraperitoneal injection,once a day for 3 consecutive days.Ligation and perforation of the cecum were performed two hours after the last gavage.The rats were sacrificed 24 hours after the operation.The general conditions of the rats were observed,and the morphology of lung tissues were observed by HE staining.The ultrastructure of the mitochondria in the lung tissues was observed by electron microscopy.The mitochondrial Na^+-K^+-ATPase and Ca^2+-Mg^2+-ATPase in lung tissues were detected by spectrophotometer and the m RNA level of HMGB1 was detected by PCR.Results:Compared with the control group,the CLP group had obviously visible lung tissue structure,and the number of mitochondria decreased significantly,the volume was smaller,the crest broke off and even in vacuoles,and there was inner and outer membrane injuries;the Na^+-K^+-ATPase and Ca^2+-Mg^2+-ATPase and SOD activity decreased significantly(P<0.01),the MDA content and HMGB1 m RNA expression level increased significantly(P<0.01).Compared with the CLP group,the lung tissue and mitochondrial ultrastructural damage was reduced,the Na^+-K^+-ATPase and SOD activity were increased(P<0.05),the MDA content and HMGB1 mRNA expression levels were significantly decreased in the YTD group(P<0.05).Conclusion:By down-regulating HMGB1 level and preventing further mitochondrial damage,Yantiao Decoction can effectively reduce lung tissue damage in ALI rats with sepsis.

关 键 词：脓毒症 急性肺损伤 HMGB1 线粒体 炎调方 大鼠 

分 类 号：R285.5[医药卫生—中药学]