Quercetin inhibits left ventricular hypertrophy in pressure-overload rats by regulating the SIRT1/NF-кB pathway

Abstract:

Objective：To investigate the protective effect of quercetin against left ventricular hypertrophy in overload-pressure rats and possible mechanism through an animal experiment. Methods：Abdominal aorta coarctation（AAC） was performed to establish a rat model of left ventricular hypertrophy. After modeling，40 Sprague-Dawley rats were randomly divided into sham-operation group，AAC group，quercetin group，and EX527 group，with 10 rats in each group. The rats in the sham-operation group and the AAC group were given normal saline by gavage and intraperitoneal injection every day，those in the quercetin group were given 50 mg/（kg·d） quercetin by gavage and intraperitoneal injection of normal saline every day，and those in the EX527 group were given intraperitoneal injection of 5 mg/（kg·d） EX527，an SIRT1 specific inhibitor，and 50 mg/（kg·d） quercetin by gavage every day. After 4 weeks of intervention，heart mass index was calculated；echocardiogra－phy was performed to evaluate cardiac function and left ven－tricular posterior wall thickness；Masson staining was performed to observe the degree of myocardial fibrosis；immunohistochem－ical staining and Western blot were used to measure the protein expression of collagen type Ⅰ（ColⅠ），collagen Ⅲ（ColⅢ），silent information regulator 1（SIRT1），and nuclear factor-?资B（NF-?资B）. Results：Quercetin increased the protein expression of SIRT1（1.000±0.000 in the sham-operation group，0.364±0.071 in the AAC group，1.138±0.070 in the quercetin group，and 0.293±0.092 in the EX527 group；F=240.539，P=0.000） and reduced heart mass（1.139±0.053 in the sham-operation group，1.300±0.056 in the AAC group，0.998±0.085 in the quercetin group，and 0.924±0.054 in the EX527 group；F=47.296，P=0.000），left ventricular posterior wall thickness（1.587±0.136 in the sham-operation group，2.657±0.355 in the AAC group，1.800±0.200 in the quercetin group，and 2.700±0.306 in the EX527 group；F=37.304，P=0.001），and the degree of myocardial fibrosis（8.515±1.343 in the sham-operation group，23.832±1.095 in the AAC group，13.260±0.674 in the quercetin group，and 24.162±1.312 in the EX527 group；F=278.741，P=0.000）. It also reduced the protein expression of ColⅠ（1.000±0.000 in the sham-operation group，3.132±0.372 in the AAC group，1.556±0.164 in the quercetin group，and 2.819±0.368 in the EX527 group；F=82.083，P=0.000），ColⅢ（1.000±0.000 in the sham-operation group，2.395±0.437 in the AAC group，1.583±0.287 in the quercetin group，and 2.434±0.461 in the EX527 group；F=23.608，P=0.024），and NF-?资B（1.000±0.000 in the sham-operation group，5.498±0.642 in the AAC group，3.637±0.715 in the quercetin group，and 5.125±0.682 in the EX527 group；F=79.912，P=0.005）. The use of EX527 reduced the protein expres－sion of SIRT1（P=0.000），increased heart mass，left ventricular posterior wall thickness，and degree of myocardial fibrosis（P=0.001，P=0.000，P=0.000），and upregulated the protein expression of ColⅠ，ColⅢ，and NF-?资B（P=0.001，P=0.024，P=0.023）. Conclusion：Quercetin can reduce the degree of left ventricular hypertrophy in overload-pressure rats，possibly by regulating the SIRT1/NF-?资B pathway.