Effect of liraglutide on myocardial remodeling in hypertensive rats
Objective To observe the effect of liraglutide on myocardial remodeling in hypertensive rats,and investigate the role of interleukin-6(IL-6)/signal transducer and activator of transcription 3(STAT3).Methods Forty Wistar rats with spontaneously hypertension were randomly divided into hypertension group,liraglutide group,activator group and liraglutide+activator group,with 10 rats each,and another 10 Wistar rats with normal blood pressure were as controls(control group).The rats in liraglutide group were subcutaneously injected with liraglutide 0.4 mg/(kg·d),the rats in activator group were intraperitoneally injected with STAT3 activator colivelin 1 mg/(kg·d),and the rats in liraglutide+activator group were intraperitoneally injected with liraglutide 0.4 mg/(kg·d)+colivelin 1 mg/(kg·d),and the rats in hypertension group and control group were injected with 1 mL of normal saline subcutaneously and intraperitoneally every day,totally for 12 weeks.The systolic blood pressure,diastolic blood pressure,cardiac indexes and left ventricular indexes were measured.The levels of IL-1β and tumor necrosis factor-α(TNF-α)in myocardial tissues were detected by ELISA,and the collagen volume fraction(CVF)in myocardial tissues was detected by Masson staining.Real-time fluorescence quantitative PCR was used to detect the relative expressions of type Ⅰ and Ⅲ collagen mRNAs in myocardial tissues.The relative expressions of type Ⅰ collagen,type Ⅲ collagen,IL-6,IL-1β,TNF-α,p-STAT3 and STAT3 proteins in myocardial tissues were detected by Western blot method.p-STAT3/STAT3 was calculated.Results The systolic blood pressures[(189.55±19.06),(153.72±13.48),(208.51±19.33),(171.14± 15.62)mmHg],diastolic blood pressures[(158.34±13.70),(122.18±11.77),(173.53±16.84),(143.70± 13.57)mmHg],cardiac indexes[(0.43±0.04)％,(0.36±0.03)％,(0.47±0.04)％,(0.39±0.03)％],left ventricular indexes[(0.36±0.04)％,(0.25±0.03)％,(0.40±0.03)％,(0.31±0.04)％],IL-1 β levels[(93.13± 11.52),(55.89±9.40),(123.49±15.04),(73.48±7.32)ng/L],TNF-α levels[(125.29±11.57),(88.34±9.32),(159.46±14.90),(103.58±12.33)ng/L]and CVFs[(28.47±4.50)％,(9.36±1.22)％,(43.69±9.53)％,(16.74±5.67)％]in hypertension group,liraglutide group,activator group and liraglutide+activator group were higher than those in control group[(128.39±12.57)mmHg,(108.42±8.55)mmHg,(0.32±0.04)％,(0.20±0.03)％,(35.69+6.33)ng/L,(50.67+8.44)ng/L,(2.04+0.58)％],the relative expressions of collagen type Ⅰ mRNA,collagen type Ⅲ mRNA,collagen type Ⅰ protein,collagen type Ⅲ protein,IL-6 protein,IL-1β protein and TNF-αprotein as well as p-STAT3/STAT3 ratios were higher in hypertension group,liraglutide group,activator group and liraglutide+activator group than those in control group(P＜0.05),and all these above indexes were higher in activator group than those in hypertension group,liraglutide group and liraglutide+activator group(P＜0.05),higher in hypertension group than those in liraglutide group and liraglutide+activator group(P＜0.05),and higher in liraglutide+activator group than those in liraglutide group(P＜0.05).Conclusion Liraglutide can reduce collagen deposition and inflammatory response,improve myocardial remodeling,and lower blood pressure in hypertensive rats,possibly by inhibiting IL-6/STAT3 signaling pathway.
hypertensionmyocardial remodelingliraglutideinterleukin-6signal transducer and activator of transcription 3rats
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