Mechanism Of The Inhibitory Effect Of Taurine On Right Ventricular Hypertrophy In Broilers Under Low Ambient Temperature

Pathological myocardial hypertrophy has been a potentially difficult metabolic disease for the modern broiler breeding industry,not only threatening the health of the broiler population,but also having an important impact on the economy of the breeding industry.Pathological myocardial hypertrophy is often accompanied by cardiomyocyte apoptosis,and calpain-1-mediated apoptosis pathway plays an important role in cardiomyocyte apoptosis.Taurine has been shown to attenuate apoptosis by inhibiting calpain-1 activity and also has antioxidant,anti-apoptotic,and cardiac health functions.This experiment was designed to determine whether taurine can prevent myocardial hypertrophy by inhibiting the apoptosis pathway of calpain-1/cytochrome c.In addition,H9c2 cardiomyocyte hypertrophy was induced in vitro by isoproterenol?ISO?to further explore the specific factors regulated by taurine in the calpain-1/cytochrome c apoptosis pathway.In vivo experiments,1%taurine was dissolved in the drinking water of broilers,and they were raised at 10°C to 12°C from the 21st day to the 42nd day.Right ventricular tissues were collected at 21,28,35 and 42 days.The results showed that taurine could reduce the expression of right ventricular hypertrophy index?RVHI?,angiotensin??Ang??,norepinephrine?NE?and cardiac hypertrophy markers atrial natriuretic peptide?ANP?m RNA levels.Taurine significantly inhibits cardiomyocyte apoptosis by maintaining mitochondrial membrane potential?MMP?and reduces the activation of caspase-9 and caspase-3 in the right ventricle of broilers.Antioxidant measurements showed that taurine enhanced the total antioxidant capacity?T-AOC?of superoxide dismutase?SOD?and the activity of glutathione peroxidase?GSH-Px?,as well as glutathione Peptide?GSH?/glutathione disulfide?GSSG?ratio.Real time PCR and Western-Blot results showed that taurine could also down-regulate the expression of calpain-1and cytoplasm c in RVH broiler myocardial cells,while up-regulating the expression of Bcl-2/Bax and mitochondrial cytochrome c.In vitro experiments show that taurine can inhibit ISO-induced increase in the surface area of H9c2 cardiomyocytes and reduce the protein expression levels of cardiac hypertrophy markers ANP,brain natriuretic peptide?BNP?and?-myosin heavy chain??-MHC?.Taurine also reduces ROS,intracellular Ca²⁺overload,and maintains mitochondrial membrane MMP stability.In addition,taurine reduces protein expression of calpain-1,Bax,t-Bid,cytochrome c,Apaf-1,cleaved caspase-9 and caspase-3,and enhances calpastatin and calpastatin.Bcl-2 protein expression inhibits cardiomyocyte apoptosis.Calpain-1 small interfering RNA?siRNA?transfection test shows that taurine can inhibit mitochondrial-dependent apoptosis by regulating the activation of calpain-1 and caspase-9 during cardiac hypertrophy,but not through calpain-1/AIF pathway inhibits cardiac hypertrophy.Therefore,we believe that taurine can prevent cardiac hypertrophy by inhibiting oxidative stress,intracellular Ca²⁺overload,calpain-1-mediated mitochondrial-dependent apoptosis pathway,and the activation of caspase-9.In summary,we found that taurine can prevent cardiac hypertrophy caused by low ambient temperature in broilers by enhancing the antioxidant capacity of cardiomyocyte and inhibiting mitochondria-dependent cardiomyocyte apoptosis.