甘草甜素抑制HMGB1/RAGE信号通路对细菌性脑膜炎大鼠神经损伤的影响

Effect of glycyrrhizin on nerve injury in rats with bacterial meningitis by inhibiting the HMGB1/RAGE signaling pathway

目的 探讨甘草甜素抑制高迁移率族蛋白B1(HMGB1)/晚期糖基化终产物受体(RAGE)信号通路对细菌性脑膜炎(BM)大鼠神经损伤的影响。方法 取大鼠50只,随机选择10只作为对照组(CON组),其余大鼠构建BM模型并随机分为BM组、甘草甜素组(48 mg/kg)、DEX组(2.5μg/kg HMGB1/RAGE通路激活剂DEX)、甘草甜素+DEX组(48 mg/kg甘草甜素+2.5μg/kg DEX),每组均10只。各药物组大鼠每天给药1次,连续治疗2周,BM组和CON组给予等量生理盐水。实验期间观察大鼠药物神经损伤情况,根据神经缺陷评分评估神经缺陷严重程度;ELISA法检测大鼠血清炎性因子水平;HE染色检测海马组织病理学变化,TUNEL法检测神经元凋亡情况,Western blot检测HMGB1/RAGE信号通路蛋白水平。结果 与CON组相比,BM组大鼠神经元稀疏、错位,核出现皱缩现象,细胞数量减少,细胞排列紊乱,神经缺陷评分(2.03±0.16)显著下降(P<0.05),神经元凋亡率(35.35±3.63)、IL-1β、TNF-α、IL-6及HMGB1和RAGE蛋白水平均显著增加(均P<0.05);与BM组相比,甘草甜素组大鼠神经元数量增加,细胞排列整齐,神经缺陷评分(4.22±0.48)显著增加(P<0.05),神经元组凋亡率(6.78±1.01)、IL-1β、TNF-α、IL-6及HMGB1和RAGE蛋白水平均显著下降(均P<0.05)。DEX组大鼠以上指标呈现相反的趋势,即DEX消除了甘草甜素对BM大鼠神经损伤的改善效果。结论 甘草甜素可能通过下调HMGB1/RAGE通路对BM大鼠神经损伤起到改善作用。

Objective To investigate the effect of glycyrrhizin on nerve injury in rats with bacterial meningitis(BM)by inhibiting the high-mobility group protein B1(HMGB1)/receptor for advanced glycation end products(RAGE)signa-ling pathway.Methods Take 50rats,Ten rats were randomly selected as the control group(CON group),and the re-maining BM rat models were constructed.Build BM models of other rats and randomly divide them into BM group,gly-cyrrhizin group(48mg/kg),DEX group(2.5μg/kg HMGB1/RAGE pathway activator DEX),glycyrrhizin+DEX group(48mg/kg glycyrrhizin+2.5μg/kg DEX),with 10rats in each group.Rats in each drug group were administered once a day for 2consecutive weeks,while BM and CON groups were given equal amounts of physiological saline.During the ex-periment,observe the drug induced nerve damage in rats and evaluate the severity of nerve defects based on the nerve de-fect score;ELISA method was applied to detect the expression of inflammatory factors;HE staining was applied to detect pathological changes in hippocampal tissue;TUNEL method was applied to detect neuronal apoptosis;Western blot was applied to detect the expression of HMGB1/RAGE signaling pathway proteins.Results Compared with the CON group,the neurons in rats in BM group were sparse and misaligned,with nuclear shrinkage,reduced cell count,disordered cell arrangement,and a obvious decrease in neural defect scores(2.03±0.16)(P<0.05),the apoptosis rate of neurons(35.35±3.63),the levels of IL-1β,TNF-α,IL-6,the protein levels of HMGB1,and RAGE were obviously increased(P<0.05);compared with the BM group,the number of neurons in rats in glycyrrhizin group increased,and the cells were ar-ranged neatly,the neurological deficit score(4.22±0.48)obviously increased(P<0.05),the apoptosis rate of neurons(6.78±1.01),the levels of IL-1β,TNF-α,IL-6,the protein levels of HMGB1,and RAGE were obviously reduced(P<0.05);the DEX group showed an opposite trend in the above indicators;DEX eliminated the improvement effect of glycyrrhizin n nerve injury in BM rats.Conclusion Glycyrrhizin may improve nerve injury in BM rats by down-regulating the HMGB1/RAGE pathway.