Objective To investigate the effect of electroacupuncture on nutritional obese mice through TLR5-gut microbio-ta pathway,and the underlying mechanism.Methods A total of 60 SPF C57BL/6 mice were selected.Among them,10 blank mice were assigned to normal group,and the nutritive obesity model was established in the other 50 mice,which was induced by high-fat diet.Twenty nutritive obesity model mice were screened and randomly divided into model group and electroacupuncture group,with 10 mice in each group.The electroacupuncture group was needled at Zhongwan,Tianshu,Guanyuan and Fenglong points.And after obtaining Qi,electroacupuncture treatment was conducted on those mice for 21 days continuously.The change in differences of general indexes(body weight,Lee's index),tissue indexes(perirenal adipose-tissue mass),serum indexes[cho-lesterol(CHO),triglyceride(TG),high-density lipoprotein(HDL-C),low-density lipoprotein(LDL-C),blood glucose),molecular indexes[leptin(LEP),adiponectin(ADPN),interleukin-6(IL-6),interleukin-1β(IL-1β),tumor necrosis factor-α(TNF-α),lipopo-lysaccharide-binding protein(LBP)and cholecystokinin(CCK)]were observed.TLR5 protein distribution was detected by immu-nohistochemical reaction,and TLR5 gene expression was detected by RT-PCR.Structural differences of intestinal flora was ana-lyzed by second generation 16S rDNA gene sequencing technology.Results The body weight,Lee's index,fat mass around kid-ney,serum contents of CHO,TG,HDL-C,the contents of LEP and FFA in fat tissue,and contents of IL-6,IL-1β,TNF-α,LBP in intestinal mucosa tissue of model group were significantly higher than that of the normal group,and the content of adipocyto-kine ADP was significantly lower.After electroacupuncture treatment,those indicators were significantly improved.The protein distribution and gene expression of TLR5 in the intestinal mucosa of the model group were significantly higher than those of the normal group,and were significantly down-regulated after electroacupuncture intervention.The number of intestinal flora spe-cies in the model group was significantly lower than those in the normal group,and were significantly increased after electroacu-puncture intervention.Proportions of Bacteroidia,Gammaproteobacteria,Eggerthellacrae and Sutterellaceae were significantly increased,while proportions of Bacilli,Clostridia,Clostridiaceae and Actinobacteria were significantly decreased.Changes in gut flora were significantly reversed after electroacupuncture intervention.Conclusion Electroacupuncture has a satisfying effect in treatment of nutritional obesity.It can regulate the distribution and expression of TLR5 protein in intestinal mucosa by balancing the structure of intestinal flora,reduce the chronic inflammatory reaction of intestinal mucosa,promote lipid metabo-lism of the body,and achieve the purpose of weight loss and lipid reduction.

OBJECTIVETo study the signaling pathways associated with lipopolysaccharide (LPS)-induced inflammation in islet micro-endothelial cells (IMECs) and the mechanism of pravastatin intervention.

METHODSIMECs exposed to LPS, SB203580, pravastatin, or SB203580+pravastatin were examined for cell apoptosis with Hoechst staining and flow cytometry and for expression levels of total-p38, photophosphorylation-p38 (p-p38) and iNOS with Western blotting.

RESULTSThe apoptosis rate and expression levels of total-p38, p-p38, iNOS in IMECs all increased after LPS exposure. Pravastatin, SB203580, and their combination significantly attenuated LPS-induced enhancement of cell apoptosis and total-p38, p-p38, and iNOS expressions in IMECs.

CONCLUSIONLPS-induced inflammatory toxicity in IMECs is associated with the activation of P38MAPK and iNOS/NO signaling pathways. Pravastatin can inhibit these pathways and suppress the apoptosis and necrosis of IMECs to relieve the cell inflammatory injuries.

Animals ; Apoptosis ; Endothelial Cells ; drug effects ; metabolism ; Endothelium, Vascular ; cytology ; Inflammation ; Islets of Langerhans ; blood supply ; MAP Kinase Signaling System ; drug effects ; Mice ; Nitric Oxide Synthase Type II ; metabolism ; Phosphorylation ; Pravastatin ; pharmacology ; p38 Mitogen-Activated Protein Kinases ; metabolism