| Objective: To explore the effect of 1, 25-dihydroxy vitamin D3 on the expression of C-Jun N-terminal kinase/C-Jun(JNK/C-Jun) inflammatory pathway in the liver of Type 2 Diabetes Mellitus(T2DM) rats as well as the possible mechanisms of it. Methods: T2 DM rat models were established by feeding with high-fat and high-sugar diets and subjected to the streptozotocin(30 mg/kg) of peritoneal injection. Sprague Dawley(SD) rats were randomly divided into normal control group(NC), T2 DM group without treatment(DM) and calcitriol-treated group(VD). Calcitriol(0.03 ug·kg-1·d-1, soluble in peanut oil) was given to VD group by filling the stomach for 8 weeks, while the DM and NC group received peanut oil. After sacrifice, fasting blood glucose(FBG), fasting insulin(FINS), alanine transaminase(ALT), asparate transaminase(AST), total cholesterol(TC), triacylglycerol(TG) in serum were tested. Homeostasis model assessment of insulin resistance(HOMA-IR) was calculated. Liver histopathology was examined by hematoxylin-eosin staining. The mRNA levels of JNK, C-Jun as well as its downstream cytokines tumor necrosis factor(TNF)-α and interleukin(IL)-1β were measured by real-time fluorescence quantitative PCR. The protein expressions of them were analyzed by immunohistochemical staining and Western blotting. Results: 1. Levels of FBG, HOMA-IR, ALT, AST, TC and TG in DM group increased and FINS decreased compared with those in NC group(P <0.05). Compared with DM group, only the decrease of ALT, AST, TG and HOMA-IR were significant in VD group(P <0.05). 2. HE staining showed that in DM group liver cells appeared swelling and fatty degeneration with inflammatory cells infiltration compared with NC group, treatment with VD could alleviate the pathologic changes. 3.The mRNA and protein levels of JNK, C-Jun, TNF-α and IL-1β in DM group increased compared with those in NC group, VD down-regulated them compared with DM group(P <0.05). Conclusion: 1. Small dose of STZ intraperitoneal injection combined with high fat and high sugar diet for 16 weeks, the SD rats showed abnormal blood glucose, blood lipid, liver function, insulin level and its sensitivity. Liver cells appeared swelling and fatty degeneration with inflammatory cells infiltration. The expression of JNK/C-Jun and its downstream cytokines were up regulated. 3.The 1,25(OH)2D3 may play a role in protecting diabetes-induced liver complications by down-regulating the inflammatory pathway of JNK/C-Jun. 4. The dose of 1,25(OH)2D3 in this test showed positive influence on diabetic liver of rat. The dose of 1,25(OH)2D3 with smallest adverse effect and largest therapeutic effect still needs further study. |
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