| It has been shown that JAK/STAT signal pathway mediated by growth factors and inflamamatory fators plays a critical role in DN and this signal pathway is negatively regulated by SOCS. To clarity the molecular mechanism of DJC in treating DN, the effects of DJC on JAK/STAT/SOCS signal pathway were investigated in vivo and in vitro. This research is expected to provide enpermental basis for clinical application of DJC.Method:Time-course and dose-course of DJC on AGEs-induced MES proliferation were performed using MTT assay to determine the concentration and time point of DJC. The inflammatory factor IL-6 was detected by ELISA. The expressions of JAK2/STAT1,3/SOCS1,3 signal pathway and COX2 in MES were observed by Western blot. Model of diabetic rats was established by combination of high-sugar and high-fat diet and low-dose STZ injection in SD rats. The rats whose FBG above 16.7 mmol-L"1 were selected and randomly divided into model group (DM group), low-dose and high-dose of DJC (DJC-L group:600 mg·kg-1, DJC-H group:2000 mg·kg-1, ig.) groups, each consisting of 7-8 rats. Control group (Ctrl group) and DM group were administered equal volume of distilled water. After 8 weeks of treatment, the rats were killed and serum was separated to detect serum lipid, oxidative stress and renal function. The renal indexes were calculated. Renal tissue specimens were fixed for HE, PAS staining and immunohistochemistry; The renal inflammatory factor IL-6 was detected by ELISA; the expressions of JAK2/STAT1,3/SOCS1,3 signal pathway and COX2 in renal cortex were measured by Western blot.Results:1.0.125,0.5,2 mg·mL-1 and 12,24,48 h were determined as of DJC concentrations and time points of subsequent experiments. Compared with Ctrl group, AGEs increased IL-6 and the expressions of COX2, p-JAK2/JAK2, p-STAT1/STAT1, p-STAT3/STAT3 and SOCS3 significantly (p<0.05), but the expression of SOCS 1 did not change obviously. After DJC treatment, IL-6 was reduced, the expressions of COX2, p-JAK2/JAK2, p-STAT1/STAT1, p-STAT3/STAT3 and SOCS3 were significantly down-regulated, yet there was no obvious effect on the expression of SOCS1.2. FBG, serum lipid, renal index and oxidative stress of model group increased significantly. Renal function was reduced, glomerular volume and renal capsule cavity were enlarged. The renal inflammatory factor IL-6 and the expressions of COX2, p-JAK2/JAK2, p-STAT1/STAT1, p-STAT3/STAT3 and SOCS3 increased significantly in DM rats. After 8 weeks of treatment, serum lipid was decreased in DJC groups, but there was no obvious difference in FBG between DJC groups and model group. DJC improved the renal function and the morphology obviously. IL-6 and the expressions of p-JAK2/JAK2, p-STAT1/STAT1, p-STAT3/STAT3, SOCS3 in renal cortex were significantly down-regulated, but the expression of SOCS1 did not change obviously.Conclusion:1. DJC improves AGEs-induced inflammation in MES by regulating JAK2/STAT3/SOCS3 signal pathway.2. DJC ameliorates STZ induced-diabetic nephropathy by regulating the JAK2/STAT3/SOCS3 signaling pathway... |
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