Effect Of Atorvastatin On The JAK/STAT Signaling Pathway And SOCS1 In Renal Tissue Of The Diabetic Nephropathy Rats

Objective: To investigate the effects of atorvastatin on the JAK-STAT-SOCS regulating mechanism in the diabetic nephropathy rats. It is expected to provide the inflammation mechanism of to the pathogenesis, and the prevention and cure of diabetic nephropathy.Methords: 60 Wistar rats were divided randomly into three groups: normal control (control group), DN control (model group), atorvastatin treated group, 20 rats in each group. The rat models were induced by right nephrectomy and intraperitoneal injection of low-dosage streptozotocin (50mg/kg). Atorvastatin (8mg/kg/d) was administrated by gavage for 12 weeks. At 2-week and 12-week, body weight, the microalbuminuria (MALB-U), the urinary protein quantity in 24h (24hUpr), serum creatinine (Scr) and urea nitrogen (BUN) were measured respectively. HE and PAS staining was used to observe morphological changes of renal tissue, and expression levels of p-STAT3, p-JAK2, SOCS1 in renal tissue of rats detected by immunohistochemistry.Results: Blood glucose in rats model group increased three-day after injection streptozotocin. After 2 weeks the MALB-U and 24hUpr increased in the rats of model group, while Scr, BUN in the rats of model group had no significant change compared with those in the control rats. 12 weeks MALB-U, 24hUpr, Scr, and BUN in the rats of model group had significant change compared with those in the control group (respectively, P<0.05). Renal pathology showed model group slightly enlarged glomerular in 2-week and increased mesangial matrix, mesangial area widened in 12-week. Pretreatment with atorvastatin relieved the renal pathology injury of model group, which mechanism may be involved in the inhibition of p-STAT3, p-JAK2, SOCS1 expression. Glomerular sclerosis and tubular damage were reduced. Immunohistochemistry staining showed that p-STAT3, p-JAK2, SOCS1 were weakly expressed in control group. While in model group, the expressions of p-STAT3, p-JAK2, SOCS1 in 2-week were higher significantly than those in control group (respectively, P<0.05). The expressions of p-STAT3, SOCS1 slightly decreased in 12 week than those in 2 week, but had no significant difference(respectively, P>0.05). While the level of p-JAK2 progressively increased with duration of diabetes and was higher than that of the control group. After treatment of atorvastatin, the expression of SOCS1 of renal tissue in treatment group was higher significantly compared with model group in the same period (respectively, P<0.05), the expressions of p-STAT3 and p-JAK2 of renal tissue in treatment group were lower compared with those of model group in the same period (respectively, P<0.05). Conclusion: Atorvastatin could reduce glomerular damage in DN, which mechanism may be involved in the in the inhibition of JAK-STAT-SOCS regulating mechanism.