基于脑肠轴探讨益气活血化浊解毒方对脑缺血再灌注损伤大鼠的影响OA北大核心CSTPCD

Objective:To investigate effect of Yiqi Huoxue Huazhuo Jiedu Prescription(YHHJP)on inflammatory factors of brain tissues,tight junction between brain and colon tissues,intestinal flora and bacterial metabolites in cerebral ischemia reperfusion injury(CIRI)rats based on brain-gut axis.Methods:Fifty male SD rats of SPF grade were randomly divided into sham-operation group(Sham),model group(MCAO),low,medium,high doses YHHJP groups(TCM-L/TCM-M/TCM-H).Middle cerebral artery occlusion model was established according to Zea Longa methods.Neurological function defects were detected 3 days after administra-tion.TTC staining was used to calculate infarct size of brain tissue.Pathological changes of brain tissue were observed by Nissl staining,and pathological changes of brain and colon tissues were observed by HE staining.IL-1β,IL-6,TNF-α in brain tissue and LPS con-tent in serum were detected by ELISA,and D-LA content in serum was detected by biochemical method.Gene expressions of ZO-1 and Claudin-5 in brain tissue and gene expressions of ZO-1,Claudin-1 in colon tissue were studied by Real-time fluorescent quantita-tive PCR.Intestinal flora were detected by 16S rDNA high-throughput sequencing.Results:Compared with Sham group,pathological damage of brain and colon tissue were serious in MCAO group,intestinal flora structure was significantly different,neural function im-pairment was aggravated,infarct size was increased,IL-1β,IL-6,TNF-α contents in brain tissue,and LPS,D-LA contents in serum were increased,gene expressions of ZO-1 and Claudin-5 in brain tissue and gene expressions of ZO-1 and Claudin-1 in colon tissue were decreased significantly(P<0.05).Compared with MCAO group,pathological damage of brain and colon tissue of rats were relieved in TCM-L,TCM-M,TCM-H groups,disturbance of intestinal microflora microecology was improved,neurological function impairment and infarct size were markedly decreased,IL-1β,IL-6,TNF-α contents in brain tissue were decreased,gene expressions of ZO-1 and Claudin-1 in colon tissue were increased significantly(P<0.05);LPS and D-LA contents in serum were decreased in YH-HJP medium and high doses groups,while gene expressions of ZO-1 and Claudin-5 in brain tissue were increased significantly(P<0.05).Conclusion:YHHJP has a good effect on improving CIRI,whose mechanism may be related to regulating diversity of intestinal flora,reducing release of intestinal bacterial metabolites LPS and D-LA,increasing gene expressions of tight junction proteins ZO-1,Claudin-5 and Claudin-1,and down-regulating secretion of proinflammatory cytokine.