Regulation Mechanism Of Nicotinic Acid On Apoptosis Of Rumen Epithelial Cell Induced By High Concentrate Diets In Vivo

Ruminal acidosis induced by high concentrate diets had become an important problem,which caused huge economic losses in ruminants production.Rumen epithelium damage caused by ruminal acidosis was the main factor that aggravated symptoms of ruminal acidosis to causes systemic symptoms.Nicotinic acid,an important B vitamin,had been shown helped to alleviate the symptoms of high concentrate stress.However,the effect of nicotinic acid on rumen epithelium damage had not been reported.The effects of niacin on rumen fermentation,oxidation resistance and rumen epithelial cell apoptosis in vivo were investigated in this study,to explore the mechanism of nicotinic acid in protecting rumen epithelium and regulating ruminal acidosis.9 sheep were randomly divided into 3 groups with 3 replications per group.Sheep fed with the high-forage diet(forage to concentrate ratio was 8:2,LC),the high-concentrate diet(forage to concentrate ratio was 2:8,HC),and the HC diet supplemented with800mg/kg niacin(HCN).The results showed that:(1)compared with LC group,HC group had a great shift-up of concentration for volatile fatty acid(VFA)metabolite including acetic acid,propionic acid,butyric acid and total volatile fatty acids(TVFA).Similar to the VFA,the concentration of lactic acid(LA)also was improved remarkably.It resulted in a decreased rumianl pH in HC group(P<0.01).It also had a high level of NAD,total NAD(H)and NADH/ NAD+(P<0.01)in HC group than those of HCN group.In contrast with HC group,HCN group had depressed the production of acetic acid,propionic acid,butyric acid and total volatile fatty acids(TVFA)remarkably,which slowed down pH decline(P<0.01).We still found the similar results for NAD,total NAD(H)and NADH/NAD+(P<0.01).(2)compared with LC group,HC group significantly decreased the oxidation resistance of CAT,T-SOD,GSH-PX,T-AOC and increased the activity of MDA(P<0.01).But HCN group significantly increased the oxidation resistance of CAT,T-SOD,GSH-PX,T-AOC oxidation resistance and decreased the activity of MDA(P<0.01).(3)compared with LC group,HC group significantly increased the concentration of proinflammatory cytokines IL-1?,IL-6,TNF-? and anti-inflammatory factor IL-4,IL-10 in sheep serum(P<0.01).HCN group significantly depressed the production of that of HC group(P<0.01).Compared with LC group,HC group decreased significantly the length,width and stratum corneum of rumen papilla and improved rumen epithelial cell apoptosis index(P<0.01).But HCN group were significantly lower than that of HC group(P<0.05 or P<0.01)and decreased rumen epithelial cell apoptosis index(P<0.01).(4)compared with LC group,HC group significantly increased the mRNA expression levels of Fas,Bcl-2,Bax,Caspase-3,Caspase-8,Caspase-9 and P53 in sheep rumen epithelium(P<0.01).But HCN group got the opposite results for that in HC group(P<0.01).In conclusion,the high concentrate stress could increase the production of VFA and lactic acid went up followed by pH plummeting,decrease the antioxidant ability,improve the expression of P53,Bcl-2,Bax,Fas,Caspase-3,Caspase-8 and Caspase-9,and induce rumen epithelium apoptosis by activating both the intrinsic and the extrinsic apoptosis pathways in sheep,which might involve in the rumen epithelial barrier dysfunction.After that,the toxic and harmful substances were absorbed into the blood by the rumen epithelium,which might cause systemic symptoms.Nicotinic acid could reduce change the redox state,improve the antioxidant ability,at the same time reducing the excessive production of VFA and lactic acid avoid excessive rumen pH decreased and alleviate the high concentrate stress,the expression of the P53,Bcl-2,Fas,Bax,Caspase-3,Caspase-8,Caspase-9 had been depressed finally,which depressed the apoptosis of rumen epithelial cells and protect the structure and function of rumen epithelium integrity.