The Effect Of TLR4/MyD88 On Myocardial Hypertrophy Induced By AngⅡ

Objectives:To study the expression of TLR4 and MyD88 in AngⅡ-induced cardiac myocytes and to observe the gene expression of inflammatory cytokines(IL-6,IL-1β,TNF and IFN-γ)in cardiomyocytes.TRL4 inhibitor TAK242 can inhibit Ang Ⅱ-induced cardiac hypertrophy and reduce inflammation,to explore the molecular mechanism of Ang Ⅱ-induced cardiac hypertrophy,myocardial hypertrophy and heart failure provide a new therapeutic target and method.Methods:1.Group of experiments:SPF level C57BL/6 strain 8-12 weeks male mice(body weight20-25g),a total of 30,they were randomly divided into 3 groups,each group 10 mice:Angiotensin(Ang Ⅱ)embedding pump group,angiotensin(Ang Ⅱ)embedding pump +inhibitor TAK242 group,saline immersion pump group.2.The establishment of the model of myocardial hypertrophy in mice and the intervention of TLR4 inhibitor TAK242:The Ang Ⅱ(1.3mg/kg/day)buried pump set up the model of myocardial hypertrophy,2 times a week of intraperitoneal injection inhibitor TAK242 in the Ang Ⅱ pump group and 4 weeks in the saline water pump group.3.Cardiac anatomy of mice:After 4 weeks,the heart of the mice was dissected and weighed(HW),the weight of the weighed mice(BW),and the length of the left tibia(TL)were measured.4.RT-q PCR of RNA was extracted from cardiac myocytes : The indexes of cardiac hypertrophy ANP,BNP,and β-MHC were detected,and the expressions of m RNA expression of TLR4,Myd88,inflammatory factor IL-6,IL-1β,TNF-αwere detected.Results:1.The camparison of HW/BW and HW/TLThe heart weight(HW)/ body weight(BW)and heart weight(HW)/ tibia length(TL)of Ang Ⅱ group were significantly higher than those of saline group(P <0.01)The ratio of heart weight(HW)/ body weight(BW)to heart weight(HW)/ tibia length(TL)significantly decreased(P <0.01).2.Cardiac hypertrophy markers ANP,BNP,β-MHC m RNA detection.The levels of ANP,BNP and β-MHC in Ang Ⅱ group were significantly higher than those in saline group(P <0.01),which were significantly different from those in Ang Ⅱgroup(P <0.01)3.Inflammatory cytokines IL-1β,TNF-α m RNA detection.Compared with the saline pump group,the inflammatory response was significantly increased in the Ang Ⅱ group(P <0.01),which was significantly different from that in the Ang Ⅱ-imbibition pump + inhibitor TAK242 group(P <0.01).4.TLR4,My D88 m RNA detection.The expression of TLR4 and My D88 in Ang Ⅱ group was significantly higher than that in saline group(P <0.01),which was significantly different from that in Ang Ⅱ group(P <0.01).5.StatisticsAll data were expressed with mean standard deviation,statistical difference P<0.05 thought the difference was statistically significant,and the difference of each group was detected by Graphpad Prism and SPSS software.Conclusions:1.AngⅡ-induced cardiac hypertrophy,TLR4,MyD88 m RNA expression increased,TLR4 / Myd88-induced Ang Ⅱ-induced cardiac hypertrophy.2.TAK242 can inhibit heart function by inhibiting TRL4 / MyD88 to further inhibit Ang Ⅱ-induced cardiac hypertrophy and inflammation.