| Objective:To study the effect of resveratrol(RES)on left ventricular remodeling in spontaneous hypertension rat(SHR)and its role in silent information regulation 2 homolog 1(SIRT1)/nuclear transcription factor-κB(NF-κB)signaling pathway.Methods:8 male Wistar-Kyoto rats(WKY)aged 8 weeks were taken as the normal group(N group).40 male SHR aged 8 weeks were randomly divided into model of hypertension group(S group),RES group(R group),EX527 group(Egroup),RES+EX527 group(R+E group),RES+pyrrolidine dithiocarbamate(PDTC)group(R+P group),with 8 rats in each group.R group was treated with RES 50 mg/(kg·d)intervention.E group was treated with EX527 5 mg/(kg·d)intervention.R+E group was treated with RES 50 mg/(kg·d)and EX527 5 mg/(kg·d)intervention,R+P group was treated with RES 50 mg/(kg·d)and PDTC100 mg/(kg·d)intervention.The general condition of the rats was observed every day during the experiment,and the body weight and systolic blood pressure(SBP)were measured every 2 weeks.After 12 weeks of intervention,left ventricular hypertrophy was measured by echocardiography and cardiac function was evaluated.After that,the rats were killed and weighed left ventricular mass and calculated left ventricular mass index(LVMI).Morphological changes of the hearts were observed by HE and Masson staining and collagen volume fraction(CVF)was measured.The levels of reactive oxygen species(ROS),malondialdehyde(MDA)and superoxide dismutase(SOD)in myocardial tissue were determined by ELISA.The expressions of proteins of SIRT1,NF-κB,transforming growth factor-β1(TGF-β1),tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6)were detected by Western blot.Results:At the end of the experiment,the SBP of rats in all SHR groups was significantly higher than that of the N group(P<0.05),and there was no significant difference in SBP between the all SHR groups(P>0.05).At the end of the experiment,the SBP of rats in the N group was not significantly higher than that before the experiment(P>0.05).There was no significant difference in body weight between all the groups(P>0.05).Compared with the N group[LVMI(2.12±0.10)mg/g,CVF(0.18±0.09)%,ROS(293.94±36.67)U/m L,MDA(3.95±0.28)nmol/m L,SOD(222.56±13.90)U/m L,protein expression:SIRT11.40±0.05,NF-κB 0.46±0.06,TGF-β1 0.33±0.04,TNF-α 0.41±0.08,IL-6 0.44±0.10],LVMI and CVF in the S group[LVMI(3.07±0.07)mg/g,CVF(2.60±0.56)%,ROS(456.22±25.55)U/m L,MDA(5.59±0.40)nmol/m L,SOD(152.50±15.22)U/m L,protein expressions:SIRT1 0.78±0.08,NF-κB 1.41±0.08,TGF-β11.44±0.11,TNF-α 1.32±0.07,IL-6 1.32±0.04] were significantly increased(P<0.05),cardiac ultrasound indicated significant left ventricular hypertrophy,the myocardial hypertrophy,myocardial fiber necrosis and fibrosis were observed under the microscope,ROS,MDA and the protein expressions of NF-κB,TGF-β1,TNF-α and IL-6 were significantly increased(P<0.05),and SOD and SIRT1 protein expression were significantly decreased(P<0.05).Compared with S group,left ventricular hypertrophy and myocardial fibrosis degree in R group[LVMI(2.72±0.09)mg/g,CVF(1.10±0.30)%,ROS(420.26±23.84)U/m L,MDA(4.98±0.49)nmol/m L,SOD(192.40±15.15)U/m L,protein expressions:SIRT10.99±0.07,NF-κB 0.98±0.12,TGF-β10.86±0.10,TNF-α 0.95±0.12,IL-6 0.99±0.11] were significantly ameliorated,SOD and SIRT1 protein expression were increased(P<0.05),LVMI,CVF,ROS,and the protein expressions of NF-κB,TGF-β1,TNF-α and IL-6 were significantly decreased(P<0.05),MDA was decreased a little,but the difference was not statistically significant(P>0.05).Compared with S group,the degree of left ventricular hypertrophy and myocardial fibrosis of E group[LVMI(3.18±0.08)mg/g,CVF(2.83±0.98)%,ROS(515.98±31.64)U/m L,MDA(6.34±0.24)nmol/m L,SOD(113.50±15.32)U/m L,protein expressions:SIRT1 0.60±0.02,NF-κB 1.68±0.07,TGF-β1 1.80±0.11,TNF-α 1.54±0.18,IL-6 1.57±0.08] showed a tendency of aggravation,LVMI,ROS,MDA and the protein expressions of NF-κB,TGF-β1,TNF-α and IL-6 increased(P>0.05),SOD and SIRT1 protein expression decreased(P<0.05),CVF increased a little,but the difference was not statistically significant(P>0.05).Compared with R group,R+E group[LVMI 2.87±0.08 mg/g,CVF(1.90±0.59)%,ROS(433.28±24.83)U/m L,MDA(5.37±0.25)nmol/m L,SOD(166.08±25.79)U/m L,protein expressions:SIRT1 0.82±0.05,NF-κB 1.14±0.16,TGF-β1 1.15±0.13,TNF-α 1.11±0.09,IL-6 1.22±0.09] showed a tendency to reverse the amelioration of left ventricular remodeling by RES,LVMI,CVF and the protein expressions of TGF-β1,TNF-α and IL-6 were increased(P<0.05),SIRT1 protein expression was decreased(P<0.05),ROS,MDA and NF-κB protein expression were increased a little,and SOD was decreased a little,but these differences were not statistically significant(P>0.05).Compared with R group,R+P group[LVMI(2.50±0.11)mg/g,CVF(0.57±0.34)%,ROS(376.64±28.25)U/m L,MDA(4.48±0.30)nmol/m L,SOD(209.02±16.45)U/m L,protein expressions:SIRT1 0.99±0.09,NF-κB 0.59±0.06,TGF-β1 0.55±0.15,TNF-α 0.78±0.11,IL-6 0.67±0.14] showed a tendency to ameliorate the degree of left ventricular hypertrophy and myocardial fibrosis more,SIRT1 protein expression showed no significant difference(P>0.05),LVMI,CVF,ROS and protein expressions of NF-κB,TGF-β1 and IL-6 significantly decreased(P<0.05),SOD increased a little,MDA and TNF-α protein expression decreased a little,but these differences were not statistically significant(P>0.05).Conclusion:RES can reduce left ventricular hypertrophy and myocardial fibrosis in SHR,and thus ameliorate left ventricular remodeling.The mechanism may be related to regulation of SIRT1/NF-κB pathway,reduction of oxidative stress and inflammatory response injury. |
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