Protective Effect Of Taurine On Liver Injury In Heat-stressed Dairy Cows And Its Mechanism

Liver dysfunction and damage caused by heat stress in summer are important factors that affect production performance,immune function and economic benefits of dairy cows.Normal operation of the liver and good liver function are the prerequisites and basic guarantees for high-quality milk and high-yield dairy cows.The purpose of this experiment was to explore the protective effect and mechanism of taurine on liver injury in heat-stressed dairy cows.Firstly,the effect of heat stress on the production performance and liver function of dairy cows was studied.16 healthy early lactating Holstein cows with similar age(4～5 years),body condition,parity(2～5)and lactation(50～120 days)were selected.Among them,8 cows were in the control group(Temperature-humidity index,THI<72)and 8 were in the heat stress group(THI>72).The pre-test period was 10 days and the formal test period was 30 days.Secondly,the protective effect and mechanism of taurine on heat stress liver injury were studied through mice model.36 ICR lactating 5～7 days mice were selected and classified into 3groups:control group(Con group),heat stress group(HS group)and heat stress+taurine group(HT group),with 12 mice in each group.The ambient temperature of the Con group was controlled as:25±0.5℃;the ambient temperature of the HS group and the HT group was controlled as:39±0.5℃,2h/d,continuous treatment for 9 days.The relative humidity of each group remained the same,both were 55±5%.The HT group was given100 mg/kg body weight taurine.The test results are as follows:(1)The results of environmental parameters and production performance showed that during the experiment of dairy cows,the daily mean THI of the HS group was more than 72,the fluctuation range was 72～83,and the average THI was 78.02±0.43.The daily average THI of the control group was less than 69,the fluctuation range was 56～69,and the mean THI was 62.68±0.69.Summer heat stress significantly reduced milk yield,milk fat percentage and total solids,and significantly increased somatic cell count(P<0.05).(2)The results of inflammatory index,antioxidant index and expression level of heat shock protein in dairy cows showed that the levels of inflammatory factors IL-1β,IL-6,TNF-αand MPO in milk of HS group were significantly higher than those of control group(P<0.05).Plasma levels of lipid peroxidation products MDA were significantly higher(P<0.001),SOD,T-AOC,GSH-P_Xand CAT levels were significantly lower(P<0.001),and HSP72,HSP90 and HSC70 protein expression levels were significantly higher(P<0.01)in HS group compared with Con group.(3)The results of liver metabolism and liver function of dairy cows showed that HS caused a significant decrease in plasma Glu levels(P<0.001),a significant increase in TG,ALT,AST,ALP and LDH levels(P<0.05)and no significant changes in TC and ALB levels(P>0.05)in cows.(4)The results of liver histomorphology and liver function of lactating mice showed that compared with the control group,the structure of hepatic lobule was blurred,the permeability of hepatocyte membrane was increased,and extensive hepatocyte balloon degeneration,diffuse necrosis and congestion appeared in HS group.After the addition of taurine,the thermal stress-induced liver damage was ameliorated.In addition,the serum levels of LDH,ALB,ALT,AST and ALP were significantly higher in HS group than those of Con group(P<0.05),while all other levels decreased significantly in HT group compared with the HS group(P<0.05)except for no significant change in ALB levels(P>0.05).(5)The results of inflammatory,antioxidant indexes and heat shock protein expression in the liver of lactating mice showed that the levels of liver TNF-α,IL-1β,IL-6 and MPO in HS group were significantly higher than those in Con group(P<0.001),while the levels in the HT group were significantly lower than those in the HS group(P<0.01).Under heat stress conditions,taurine supplementation significantly decreased the content of MDA(P<0.001)and increased the activities of antioxidant enzymes T-AOC,SOD and CAT in liver(P<0.01).In addition,heat stress significantly increased HSP72 and HSP90 protein expression(P<0.001)and decreased HSC70 protein expression(P<0.001)in lactating mice compared with the Con group,and after taurine supplementation,HSP72 and HSP90 protein expression significantly decreased(P<0.001)and HSC70 protein expression significantly increased(P<0.001).(6)The results of taurine synthesis and transporter protein expression in lactating mice showed that the protein expression levels of Tau T,CDO and CSD in the liver of HS group were significantly lower than those of the Con group(P<0.001),while the addition of taurine significantly increased the expression levels of these proteins(P<0.01).(7)The results of liver NLRP3 inflammasome activation,hepatocyte pyroptosis and HMGB1/NLRP3 pathway protein expression levels in lactating mice showed that compared with the control group,the expression of NLRP3 inflammasome in HS group was significantly up-regulated,the hepatocyte pyroptosis of HS group was significantly increased(P<0.001),and the protein expressions of HMGB1,NLRP3,ASC,Pro-caspase1,Cleaved-caspase1,Pro-IL-1β,IL-1βand GSDMD-N in HS group were significantly increased(P<0.001).Taurine could significantly inhibit the activation of NLRP3 inflammasome,reduce hepatocyte pyroptosis(P<0.001)and inhibit the expression of HMGB1/NLRP3 pathway protein(P<0.05).In conclusion,heat stress leads to oxidative stress and systemic inflammatory response in dairy cows,affects liver metabolism and liver function,and reduces the lactation performance of dairy cows.Taurine supplementation can improve the body’s anti-stress ability,liver inflammatory damage and oxidative damage,and can reduce hepatocyte pyroptosis and sterile inflammation by inhibiting HMGB1/NLRP3 signaling pathway,protect liver tissue structure and function which alleviates liver injury caused by heat stress.