矿物药青礞石对戊四氮点燃癫痫大鼠血清中IL-1β和IL-2等细胞因子水平的影响

Effects of Chloriti Lapis on Serum Levels of Cytokines in Epileptic Rats

目的:研究青礞石对戊四氮(pentylenetetrazol,PTZ)点燃癫痫大鼠血清中炎症细胞因子表达水平的影响。方法:利用PTZ腹腔注射制备慢性癫痫大鼠模型,实验分为对照组、模型组、阳性药卡马西平组、青礞石低剂量组和青礞石高剂量组。大鼠腹主动脉取血,采用酶联免疫吸附法(ELISA)测定血清中白细胞介素-1β(IL-1β)、IL-2、IL-6、肿瘤坏死因子-α(TNF-α)、γ-干扰素(IFN-γ)、高迁移率族蛋白B-1(HMGB-1)及超敏C反应蛋白(hs-CRP)水平,并对各细胞因子之间及其与PTZ点燃癫痫大鼠结肠肠道微生物的相关性进行分析,利用SPSS 18.0对结果进行统计学分析。结果:与对照组比较,模型组大鼠血清中IL-1β、IL-2、IL-6、TNF-α及hs-CRP水平均显著升高(P<0.01)。与模型组比较,青礞石高、低剂量给药组大鼠血清中各细胞因子水平显著下降(P<0.05,P<0.01)。细胞因子相关性分析结果表明,IL-2与IL-6呈显著正相关(P<0.05),IL-6与TNF-α、hs-CRP呈显著正相关(P<0.05,P<0.01),TNF-α与hs-CRP呈显著正相关(P<0.01),IFN-γ与HMGB-1呈显著正相关(P<0.05)。细胞因子与肠道菌群相关性分析结果表明,疣微菌门、Akkermansia菌属与炎症因子IL-6、TNF-α、hs-CRP间呈显著相关性(P<0.05)。青礞石可通过影响细胞因子(IL-6、TNF-α、hs-CRP)、Akkermansia菌属对PTZ点燃癫痫大鼠起到干预作用。结论:青礞石干预PTZ点燃癫痫可能与影响IL-1β、IL-2等细胞因子,从而降低体内炎性反应有关。

Objective:To study the effect of the mineral Chinese medicine Chloriti Lapis on the levels of inflammatory cytokines in the serum of pentylenetetrazol(PTZ)-kindled epileptic rats.Methods:The rat model of chronic epilepsy was established by intraperitoneal injection of PTZ.This study designed five groups,including a control group,a model group,a positive drug(carbamazepine)group,a Chloriti Lapis low-dose group,and a Chloriti Lapis high-dose group.The levels of interleukin-1 beta(IL-1β),IL-2,IL-6,tumor necrosis factor-alpha(TNF-α),interferon-gramma(IFN-γ),high-mobility group box 1(HMGB-1),and high-sensitivity C-reactive protein(hs-CRP)in serum were determined by enzyme-linked immunosorbent assay(ELISA)after collection of abdominal aorta blood from the rats.Correlation analysis was conducted between cytokines as well as between cytokines and the colonic microbiota of PTZ-kindled epileptic rats.Statistical analysis was performed using SPSS 18.0.Results:Compared with the control group,the model group showed elevated levels of IL-1β,IL-2,IL-6,TNF-α,and hs-CRP in serum(P<0.01).Compared with the model group,high-dose and low-dose Chloriti Lapis lowered the levels of cytokines in serum(P<0.05,P<0.01).IL-6 was positively correlated with IL-2,TNF-α,and hs-CRP(P<0.05,P<0.01).TNF-αwas positively correlated with hs-CRP(P<0.01).There was a positive correlation between IFN-γand HMGB-1(P<0.05).In addition,Akkermansia,belonging to Verrucomicrobia,was correlated with IL-6,TNF-α,and hs-CRP(P<0.05).The results confirmed that Chloriti Lapis regulated the inflammatory cytokines(IL-6,TNF-α,hs-CRP)and Akkermansia in PTZ-kindled epileptic rats.Conclusion:Chloriti Lapis may treat the PTZ-kindled epilepsy by intervening in IL-1β,IL-2 and other cytokines and mitigating the inflammatory response in vivo.