The Mechanism Of The Regulatory Role Of KB-120 On Hepatic Oxidative Damage In Murine

Liver,the largest organ in the body,plays an important role in nutrients’metabolism and transformation.Abnormal hepatic function is closely related to animal health problems.Nowadays,hepatic oxidative stress is reported to be one of the pathogenesis resulting in liver disease and animal health problems.Thus,the thesis is mainly focused on the regulatory role of KB-120 on the hepatic oxidartive stess,to provide theoretical basis for its application in animal production.The thesis is divided into two parts:1.Effects of KB-120 on HFD-induced hepatic oxidative injury in rats and offspringThe first part to explore the effects of microbiota-fermented antioxidants（KB-120）supplementation during pregnancy and lactation on the high fat diet（HFD）-induced hepatic oxidative stress and function,lipid metabolism and NLRP3 inflammasome in rats and offspring.A total of 36 female rats were randomly divided into 3 groups at the beginning of pregnancy:the control group（CG）,HFD and HFDA（HFD+2%KB-120）.Rats were slaughtered at the first and tenth day of lactation（L1and L10）and offspring were slaughtered at L10.The plasma and liver of rats,and liver of offspring were collected.The results showed that KB-120 reversed HFD-induced the activities of total and inducible nitric oxide synthase（TNOS and i NOS）and improved anti-oxidative enzymes in liver of rats and offspring.Additionally,KB-120 reduced HFD-induced lipid accumulation through improving hepatic fatty acid synthase（FAS）in rats and offspring.KB-120 decreased HFD-induced alkaline phosphatase（AKP）activity in plasma of rats,and aspartate transaminase（AST）,alanine aminotransferase（ALT）,alkaline phosphatase（AKP）activities in liver of rats and offspring.Furthermore,KB-120 reduced HFD-activated NLRP3 inflammasome in liver of rats and suppressed the gene expression of IL-1βand IL-18 in offspring.In conclusion,the present results indicated that KB-120 supplementation during pregnancy and lactation reversed HFD-induced hepatic oxidative stress,decreased lipid accumulation and NLRP3 inflammasome and improved hepatic function in rats and offspring,suggesting KB-120 can be functional ingredients to effectively improve maternal-fetal health.2.Effects of KB-120 on diquat-induced hepatic oxidative injury in mouseThe second part was aimed to explore the effects of microbiota-fermented antioxidants（KB-120）on diquat-induced hepatic oxidative damage,endoplasmic reticulum stress and apoptosis in mice.Thirty C57BL female mice weighted 16～18g were randomly divided into3 groups after adapting to the environment,10 mice in each group.Each group was fed basal diet,control group and diquat group received normal saline and KB-120 group received KB-120（0.0013 m L/g）were given through according to the weight of mice each day.After feeding 22 days,model group and KB-120 group were injected diquat（36 mg/kg）according to the body weight of mice through intraperitoneal injection,while control group was injected the same amount of saline.After diquat treatment for 3 hours,mice were slaughtered and liver samples were collected.The results showed that compared with control group,H₂O₂,MDA contents,activities of AST and ALT in diquat group were significantly increased（P<0.05）,while T-SOD activity and T-AOC level in diquat group were significantly decreased（P<0.05）;Compared with model group,H₂O₂,O₂^-,MDA concentrations and AST activity in KB-120 group were significantly decreased（P<0.05）,GSH-Px activity in KB-120 group was significantly increased（P<0.05）.The expression of NTCP in KB-120 group was significantly higher（P<0.05）than that in diquat group,indicating that liver reduced the uptake of bile salts and accelerated the metabolism of bile acids.The MRP2 in KB-120 group was significantly higher（P<0.05）than that in diquat group,while the MRP3 was significantly lower（P<0.05）than diquat group,indicating that KB-120 promoted the efflux of organic anions and bile salt circulation.Thus,KB-120 has a recovery effect on heaptic bile acid transport in mice.Compared with control group,caspase-3,caspase-8,GRP78,PERK and ATF6 gene expression in diquat group were significantly increased（P<0.05）.But the gene expression of IRE in control group was significant higher than that in diquat group（P<0.05）.Compared with diquat group,caspase-3,caspase-8,PERK and ATF6 gene expression in KB-120 group were significantly decreased（P<0.05）.The results suggested that KB-120attenuated diquat-induced antioxidant capacity endoplasmic reticulum stress and apoptosis and improved hepatic function in mice.In conclusion,KB-120 supplementation during pregnancy and lactation alleviated HFD-induced maternal-fetal hepatic free radicals production and increased antioxidative enzymes,attenuated lipid accumulation,hepatic function and NLRP3 inflammasome and cell apoptosis.KB-120 alleviated diquat-induced hetatic dysfunction,bile acid metabolism and decresed hepatic cell apoptosis and endoplasmic reticulum stress.