Effects of arbutin on myocardial fibrosis in spontaneously hypertensive rats and its mechanism

XU Yin-li; ZHAO Ji-kai; ZHAO Qiu-sheng; ZHANG Qiu; LIU Yu

doi:10.16048/j.issn.2095-5561.2023.05.06

Abstract：Objective To investigate the effect of arbutin(AR)on myocardial fibrosis in spontaneously hypertensive rats(SHR)and its mechanism.Methods Ten 10-week-old male Wistar SHRs were selected and divided into SHR group(n=5)and SHR+AR group(n=5)by random number table method.SHR+AR group was given 100 mg/(kg·d)AR by gavage for 4 weeks.Five healthy 10-week-old male Wistar rats were selected as the normal control group.The blood pressure of rat tail artery was recorded in the three groups.After the last blood pressure was recorded,echocardiography was performed to examine the cardiac function indexes of each group.Serum angiotensin Ⅱ(AngⅡ)and aldosterone levels were detected by enzyme-linked immunosorbent assay(ELISA)after 4 weeks of intragastric administration.After 4 weeks of intragastric administration,the rats were killed,the body weight(BW)of the rats was weighed,the whole heart was separated and the heart weight(HW)was weighed,and the HW/BW value was calculated.The histopathology and fibrosis of ventricular muscle were observed by hematoxylin-eosin(HE)and Masson staining.The expressions of myocardial transforming growth factor-β1(TGF-β1)and its downstream p-Smad 2/3 protein were detected by western blotting,and the expressions of fibrosis index proteins Collagen Ⅲ and Collagen Ⅰ were detected.Results Compared with the normal control group,the left ventricular diastolic end-diastolic ventricular septal thickness was significantly increased in SHR group and SHR+AR group,and the ejection fraction and fractional shortening(FS)were significantly decreased.Compared with the SHR group,ejec-tion fraction and FS in SHR+AR group were significantly increased,and the differences were statistically significant(P<0.05).At the beginning of the experiment,there was no significant difference in systolic blood pressure and diastolic blood pressure between SHR group and SHR+AR group(P>0.05).After 4 weeks of intragastric administration,the systolic blood pressure and diastolic blood pressure of SHR+AR group were significantly lower than those of SHR group,and the difference was statistically significant(P<0.05).After 4 weeks of intragastric administration,the HW/BW in SHR group and SHR+AR group was higher than that in normal control group,but the HW/BW in SHR+AR group was lower than that in SHR group,and the difference was statistically significant(P<0.05).The myocardial interfibrillar fibrosis was obvious in SHR group,and the degree of fibrosis in SHR+AR group was significantly less than that in SHR group.After 4 weeks of intragastric administration,serum AngⅡ and aldosterone in SHR group were higher than those in normal control group,while serum Ang Ⅱ and aldosterone levels in SHR+AR group were lower than those in SHR group,and the differences were statistically significant(P<0.05).Compared with the normal control group,the expressions of inflammatory associated proteins CollagenⅠ,CollagenⅢ,TGF-β1 and p-Smad2/3 in SHR group were significantly increased,while compared with the SHR group,the expressions of inflammatory associated proteins Collagen Ⅰ,Collagen Ⅲ,TGF-β1 and P-SMad2/3 in the AR+SHR group were significantly decreased,with statistical significance(P<0.05).Conclusion AR has a protective effect on the heart of SHR,and its mechanism may be realized by regulating the TGF-β/Smads pathway to play an anti-fibrotic role.