Effects Of Taurine And Taurocholic Acid On Hepatic Oxidative Stress And Inflammation In Obese Type 2 Diabetic Rats

Obese Type 2 Diabetes is a disorder of body’s glycolipid metabolism caused by obesity-induced islet cell damage.Patients often show excessive obesity and persistent hyperglycemia,accompanied by chronic damage and dysfunction of various tissues such as liver,kidney,heart,retina,and cerebrovascular,which seriously threaten human and animal health.The liver is the main site of bile and taurine synthesis,and the synthesis of bile acid and taurine is hindered when the hepatic function is impaired.Previous studies have proved that bile acid metabolism dyfunction can lead to insulin resistance and disorders of glucose and lipid metabolism,which further aggravate the occurrence of obese T2 DM.Taurine and taurocholic acid supplementation modulates bile acid-related signaling pathways in obese T2 DM rats,and has a good effect on the prevention and treatment of obese T2 DM.Bile acids and taurine not only enhance the antioxidant capacity of the body,but also inhibit the occurrence of acute and chronic inflammation,but the role of taurine and bile acids in liver damage caused by obese T2 DM is unclear.This experiment intends to induce an obese T2 DM rat model by feeding high-fat feed combined with streptozotocin(STZ)intraperitoneal injection,and taurine and taurocholic acid were added to drinking water at the same time.The effect of taurine and taurocholic acid on factors related to oxidative stress and inflammatory response in the liver was detected,which would elucidate the regulatory role of taurine and taurocholic acid in the development of obese T2 DM on liver injury and their possible mechanisms.The result will provide a theoretical basis for the application of taurine and taurocholic acid to prevent and treat liver damage caused by obese T2 DM in humans and animals.Male SD rats weighing 180-200 g were randomly divided into 4 groups,namely control group,model group,taurine group and taurocholic acid group,and the formal test was carried out after 1 week of acclimatization feeding,the prevention test was 10 weeks and the intervention test was 19 weeks,and the liver tissue and blood samples of rats were collected for the determination of relevant indexes at the end of the test.Results: 1.The morphological structure of hepatocytes in obese T2 DM rats was regular and clear after taurine and taurocholic acid treatment,the perivascular inflammatory cells were significantly reduced,and the serum ALT and AST levels were significantly decreased.The results indicated that taurine and taurocholic acid had significant preventive effects on liver injury caused by obese T2 DM.2.Liver SOD,CAT,GSH-Px and T-AOC activity were obviously increased while MDA content was significantly decreased in obese T2 DM rats after taurine and taurocholic acid treatment;Nrf2,HO-1,NQO1 and γ-GCS m RNA expression levels were remarkedly increased in the Nrf2 signaling pathway,and Nrf2 and HO-1 protein expression levels were significantly increased,indicating that taurine and taurocholic acid could improve the antioxidant capacity of the liver of obese T2 DM rats by activating the Nrf2 signaling pathway.3.The liver M1 type KCs marker CD68 m RNA expression level was significantly reduced and the M2 type KCs marker CD206 m RNA expression level was remarkedly increased in obese T2 DM rats after taurine and taurocholic acid treatment,and the ratio of CD68 to F4/80 was significantly reduced,while the ratio of CD206 to F4/80 was obviously increased.The results suggested that taurine and taurocholic acid can reduce the number of M1-type KCs and increase the number of M2-type KCs in obese T2 DM rats.4.The levels of liver M1-type polarization products IL-1β,IL-6,IL-8,IL-18,TNF-α,i NOS and NO were remarkedly reduced in obese T2 DM rats after taurine and taurocholic acid treatment;the m RNA expression levels of LBP,TLR4,My D88,NF-κB,AP-1 and IRF-3 in the LPS-TLR4-NF-κB signaling pathway were significantly reduced;NLRP3,Caspase1 and Caspase11 m RNA expression levels were obviously reduced in the NLRP3 inflammatory vesicle signaling pathway;and IFN-γ,JAK2 and STAT1 expression were remarkedly reduced in the JAK2-STAT1 signaling pathway.The results indicated taurine and taurocholic acid were able to inhibit M1-type KCs mediated pro-inflammatory response by acting on the LPS-TLR4-NF-κB,NLRP3 inflammatory vesicles and JAK2-STAT1 signaling pathways.5.The levels of liver M2-type polarization products IL-4 and IL-10 were remarkedly increased in obese T2 DM rats after taurine and taurocholic acid treatment;the m RNA expression levels of regulatory factors STAT6,PPAR-γ and SOCS1 were obviously increased,indicating that taurine and taurocholic acid could promote the polarization of M2-type KCs and their mediated anti-inflammatory responses.The results of this study indicated that taurine and taurocholic acid could improve hepatic antioxidant capacity of obese T2 DM rats by activating the Nrf2 signaling pathway,and reduce hepatic inflammatory response by inhibiting the polarization of M1-type KCs and promoting the polarization of M2-type KCs.