柴桂剂对高血脂症脑缺血再灌注损伤大鼠肠道炎症及TLR4/NF-κB信号通路的影响OA

Objective It is to explore the neuroprotective effect and its potential mechanisms of Chai Gui Decoction in rats with hyperlipidemia and brain ischemia/reperfusion injury based on Toll-like receptor 4(TLR4)/nuclear factor-κB(NF-κB)signaling pathway.Methods One hundred and twenty male rats were taken,14 of which were randomly selected as normal group,and the remaining rats were fed with high-fat diet to establish models of hyperlipidemia.84 successfully modeled rats with hyperlipidemia were randomly divided into 6 groups,with 14 rats in each group.The Chai Gui Decoction group,nimodipine group,Da Chai Hu Decoction group and Guizhi Fuling Pill group were administered corresponding drugs via gastric gavage at doses of 6.48 g/kg,20 mg/kg,4.05 g/kg,and 3.04 g/kg,respectively,the sham operation group and model group were administered equal volumes of physiological saline via gastric gavage,all administered once daily.On the 7th day of gavage,the rats of all groups except for the sham operation group were prepared with suture-occluded method to establish models of cerebral ischemia-reperfusion injury.At 6 hours after ischemia-reperfusion,each group was administered corresponding drugs or physiological saline via gastric gavage once.At 24 hours after ischemia-reperfusion,the neurological dysfunction scores of the rats were recorded,then the rats were anesthetized for blood collection.The ser-um levels of total cholesterol(TC),triglycerides(TG),low-density lipoprotein cholesterol(LDL-C)and high-density lip-oprotein cholesterol(HDL-C)were measured by biochemical analyzers,the serum levels of tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β)and TLR4 were measured by ELISA.The cerebral tissue of the rats was taken to observe the pathological morphology by HE staining,the positive expressions of TLR4 and NF-κB p65 in cerebral tissue of the ischemic side were detected by immunohistochemistry,the mRNA and protein expressions of TLR4,NF-κB p65 and IL-1β in cere-bral tissue of the ischemic side and colon tissues were detected by Real-time quantitative PCR and Western blot analysis,respectively.Results The neurological dysfunction scores of rats in all medicated groups were significantly lower than that in the model group(all P<0.05),but no statistically significant differences were observed among the medicated groups(all P>0.05).Compared with the normal group,the serum levels of TC,TG and LDL-C were significantly increased(all P<0.05),while the serum levels of HDL-C were significantly reduced in rats of the sham operation group,model group and all medicated groups(all P<0.05).Compared with the model group and nimodipine group,the serum levels of TC,TG and LDL-C were significantly reduced(all P<0.05),while the serum levels of HDL-C were significantly increased in rats of the traditional Chinese medicine treated groups(all P<0.05).Compared with the Da Chai Hu Decoction group and Guizhi Fuling Pill group,the serum levels of TC,TG and LDL-C were more lower(all P<0.05),while the serum level of HDL-C was more higher in rats of the Chai Gui Decoction group(P<0.05).Compared with the sham operation group,the brain tissue damage was obvious in rats of the model group;the serum levels of TNF-α,IL-1β and TLR4,the mean optical density values of positive expressions of TLR4 and NF-κB p65 in cerebral tissue of the ischemic side,and the mRNA and protein expressions of TLR4,NF-κB p65 and IL-1β in cerebral tissue of the ischemic side and colon tissues were signifi-cantly increased(all P<0.05).Compared with the model group,the brain tissue damage was obviously alleviated in rats of the Chai Gui Decoction group and nimodipine group;the serum levels of TNF-α,IL-1β and TLR4,the mean optical density values of positive expressions of TLR4 and NF-κB p65 in cerebral tissue of the ischemic side,and the mRNA and protein expressions of TLR4,NF-κB p65 and IL-1β in cerebral tissue of the ischemic side and colon tissues were signifi-cantly increased in rats of the medicated groups(all P<0.05),furthermore,these indicators were significantly lower in the Chai Gui Decoction group and nimodipine group than those in the Da Chai Hu Decoction group and Guizhi Fuling Pill group(all P<0.05).Conclusion Chai Gui Decoction can significantly improve neurological function and regulate blood lipid of rats with hyperlipidemia and cerebral ischemia-reperfusion injury,its protective effects may be achieved via inhibiting TLR4/NF-κB signaling pathway,reducing inflammatory responses,and regulating gut-brain axis balance.