雷公藤红素调节HMGB1/RAGE信号通路对子宫内膜炎大鼠炎症反应的影响  

Influence of celastrol on inflammatory response in endometritis rats by regulating HMGB1/RAGE signaling pathway

作　　者：魏桠楠 柴守辉[1] 王福萍 徐行丽[1] 焦贵霞[1] WEI Yanan;CHAI Shouhui;WANG Fuping;XU Xingli;JIAO Guixia(Department of Gynecology,Tengzhou Cen-tral People's Hospital,Tengzhou 277500,China)

机构地区：[1]滕州市中心人民医院妇科,滕州277500

出　　处：《中国免疫学杂志》2024年第12期2518-2524,共7页Chinese Journal of Immunology

摘　　要：目的:探究雷公藤红素(CEL)调节高迁移率族蛋白B1(HMGB1)/晚期糖基化终末产物受体(RAGE)对子宫内膜炎大鼠炎症反应的影响。方法:将72只SPF级SD雌性大鼠随机分为正常对照组(Control组)、假手术组(Sham组)、模型组(Model组)、低剂量CEL组(CEL-L组,CEL 20 mg/kg)、高剂量CEL组(CEL-H组,CEL 40 mg/kg)和HMGB1抑制剂甘草酸组(GA组,GA 2 mg/kg),每组12只。采用子宫内注射苯酚胶浆剂建立大鼠子宫内膜炎模型。HE染色观察大鼠子宫组织病理学变化;ELISA测定大鼠血清中超氧化物歧化酶(SOD)、丙二醛(MDA)、一氧化氮(NO)和前列腺素E2(PEG2)水平和大鼠子宫组织TNF-α、IL-1β水平;免疫组化检测大鼠子宫组织中MMP-2与MMP-9水平;采用RT-qPCR法检测大鼠子宫组织中HMGB1和RAGE的mRNA表达水平;Western blot检测大鼠子宫组织中HMGB1、RAGE蛋白表达。结果:与Sham组相比,Model组大鼠子宫组织损伤严重,血清SOD水平与子宫组织中MMP-2、MMP-9水平显著下降(P<0.05);血清MDA、NO、PEG2、子宫组织中TNF-α和IL-1β水平、HMGB1和RAGE mRNA及蛋白表达显著上升(P<0.05)。与Model组相比,CEL-L、CEL-H组大鼠各项指标变化与上述相反(P<0.05)。CEL-H组与GA组相应指标比较差异无统计学意义(P>0.05)。结论:雷公藤红素可能通过下调HMGB1/RAGE信号通路,减轻子宫内膜炎大鼠的炎症反应。Objective:To investigate the influence of celastrol(CEL)on the inflammatory response of rats with endometritis by regulating high mobility group box B1(HMGB1)/receptor for advanced glycation end products(RAGE).Methods:Seventy-two SPF SD female rats were randomly grouped into normal control group(Control group),sham operation group(Sham group),Model group,low-dose CEL group(CEL-L group,CEL 20 mg/kg),high-dose CEL group(CEL-H group,CEL 40 mg/kg)and HMGB1 inhibitor glycyrrhizic acid group(GA group,GA 2 mg/kg),12 rats in each group.A rat model of endometritis was established by intrauterine injection of phenol mucilage.Histopathological changes of rat uterus were observed by HE staining;the levels of superoxide dismutase(SOD),malondialdehyde(MDA),nitric oxide(NO)and prostaglandin E2(PEG2)in rat serum,and the levels of TNF-αand IL-1βin rat uterus tissue were measured by ELISA;the levels of MMP-2 and MMP-9 in rat uterus tissue were detected by immunohistochemistry;the mRNA expression levels of HMGB1 and RAGE in rat uterus tissue were detected by RT-qPCR;the protein expressions of HMGB1 and RAGE in rat uterus were detected by Western blot.Results:Compared with the Sham group,the uterine tissue of the Model group was severely damaged,and the level of serum SOD and the levels of MMP-2 and MMP-9 in the uterine tissue were obviously decreased(P<0.05);the level of serum MDA,NO,PEG2,TNF-αand IL-1β,the expressions of HMGB1 and RAGE mRNA and protein in uterine tissue were obviously increased(P<0.05).Compared with the rats in the Model group,the changes of each index of the rats in the CEL-L and CEL-H groups were opposite to the above(P<0.05).There was no obvious difference in the corresponding indexes between the CEL-H group and the GA group(P>0.05).Conclusion:Celastrol may reduce the inflammatory response in rats with endometritis by down-regulating the HMGB1/RAGE signaling pathway.

关 键 词：雷公藤红素 高迁移率族蛋白B1/晚期糖基化终末产物受体信号通路 子宫内膜炎 炎症反应 

分 类 号：R711.32[医药卫生—妇产科学]