Effect of 1,25-dihydroxyvitamin D3 on C-Jun N-terminal kinase/C-Jun inflammatory pathway in liver of type 2 diabetes mellitus rats

Abstract

Objective To explore the effect of 1,25-dihydroxy vitamin D3 (VD) 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 and the possible mechanisms. Methods Sprague Dawley(SD) rats were divided into normal control group(NC), T2DM group(DM) and calcitriol-treated group(VD) via random number table. Calcitriol was given to VD group by gavage for 8 weeks, while the DM and NC group received peanut oil. After sacrifice, body weight was measured and fasting blood glucose(FBG), alanine transaminase(ALT), asparate transaminase(AST), total cholesterol(TC), triacylglycerol(TG) in serum were tested. Liver histopathology was examined by hematoxylin-eosin (HE) staining. The mRNA levels of JNK, C-Jun and its downstream cytokines tumor necrosis factor(TNF-α) and interleukin(IL-1β) were measured by real-time fluorescence quantitative PCR. The protein expression was analyzed by immunohistochemical staining and Western blotting.The t test was performed for pair-wise comparison and wilcoxon rank sum test was used for ranked data. Results The level of FBG, ALT, AST, TC and TG in DM group increased and body weight decreased compared with those in NC group((25.7±2.3)vs(5.8±0.9) mmol/L, (137±12)vs(53±6)U/L,(162±13)vs(65±7)U/L, (1.4±0.2)vs(1.21±0.08)mmol/L, (1.32±0.15)vs(0.73±0.10)mmol/L,(362±12)vs(452±16) g; t=29.573,26.142,14.395, 10.632,11.746,9.539, respectively, all P<0.05). Compared with DM group, ALT,AST and TG decreased significantly in VD group((112±10)vs(137±12) U/L, (129±11)vs (162±13) U/L, (1.06±0.14)vs (1.32±0.15) mmol/L; t=5.382,6.043,5.268, all P<0.05). HE staining showed that liver cells were in alignment and normal in NC group, whereas appeared swelling and fatty degeneration with inflammatory cells infiltration in DM group. VD treatment could alleviate the pathologic changes. 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 treatment down-regulated this inflammatory factors compared with DM group(χ2=19.958, 20.710, 20.969, 21.255, respectively, all P<0.05). JNK was positive correlated significantly with C-Jun, TNF-α, IL-1β (r=0.857,0.821,0.836,P<0.05). Conclusion 1,25(OH)2D3 may protect diabetes-induced liver complications by down-regulating the inflammatory pathway of JNK/C-Jun. Key words: Calcitriol; Diabetes Mellitus,type 2; Liver; Inflammation