Effect Of TLR4-dependent JNK Pathway On Adipokine Of Obstractive Sleep Apnea Syndrome With Hypertension Rats

Objective: Investigating the expression of TLR4-dependent JNKpathway on obstructive sleep apnea–hypopnea syndrome（OSAHS）withhypertension, to Leptin and TNF-α.As a whole, cellular and molecular level toexplore abnormal fat metabolism, inflammation of OSAHS and the influence ofhigh blood pressure. Methods: SD male rats （48）to three groups: normalcontrol group(NC), the intermittent hypoxia8weeks group(IH8),theintermittent hypoxia6weeks group(IH6). hypoxia for8hours，in every120seconds in cabin. The rats of NC in air. tail arterial systolic pressure after theintervention. HE staining to observe each group the pathologic changes of therenal artery of rats. ELISA method to detect each group in rat plasma TNF alpha,the change of the content of Leptin,Fluorescence quantitative PCR, Western Blotmethod to detect fat tissue TLR4, JNK mRNA and protein expression. Taking intermittent hypoxia group8weeks adipose tissue of rats with the originalgeneration grow fat cells, microscope cell morphology change, oil red Ostaining, cell immunohistochemical to identify the cells. The original generationof fat cells is divided into four groups:8weeks hypoxia (8weeks group),intermittent hypoxia group8weeks lipopolysaccharide induce (LPS inducedgroup), intermittent hypoxia8weeks TLR4anesthesia group (TLR4blockgroup), hypoxia8weeks group JNK block (JNK block group). Collect the abovegroups of fat cells, to detect the expression of TLR4, JNKmRNA and protein, inaddition to collect the above each fat cells culture, using the method of ELISAdetermination of the content of TNF alpha, Leptin in culture.Result：1Modelgroup rats tail arterial pressure increased, and appeared in the wall thickening ofthe renal artery pathological changes, thus successfully established OSAHScombined hypertensive rat model.2hypoxia group six weeks,8weeks ofintermittent hypoxia group serum TNF alpha, Leptin levels higher than normalcontrol significantly (P <0.01, P <0.01), and8weeks of hypoxia group rosemore significantly (P <0.05).3hypoxia6weeks, hypoxia8weeks group fattissue TLR4, JNK mRNA and protein expression levels higher than normalcontrol significantly (P <0.01, P <0.01).4Adipocytes were cultured. Thecells could adherent grow, using cell immunohistochemical visible cytoplasmstaining in tan and red Oobserve adipocytes.5TLR4mediated JNK signalingpathways in the fat cells express: compared with the intermittent hypoxia8 weeks group, lipopolysaccharide revulsant can increase TLR4, JNK mRNA andprotein expression (P <0.05, P <0.05); TLR4blockers can down TLR4, JNKmRNA and protein expression (P <0.05, P <0.05); JNK interdicts can only cutJNKmRNA and protein expression (P <0.05), the TLR4mRNA and proteinexpression of meaningless.6OSAHS hypertension the fat cells in rat models ofTLR4mediated JNK signaling pathway of TNF alpha, Leptin secretionregulation: lipopolysaccharide revulsant than8weeks intermittent hypoxiagroup TNF alpha, Leptin secretion increased (P <0.05), TLR4blockers, JNKblockers group than intermittent hypoxia eight weeks group TNF alpha, Leptinsecretion,were reduced(P<0.05,P<0.05).Conclusion:The JNK pathway controlsthe progress of OSAHS with hypert-ension.