OBJECTIVETo study the effects of Zhenqing Recipe (ZQR) and earthworm on the expressions of transforming growth factor-beta1 (TGF-beta1) and plasminogen activator inhibitor-1 (PAI-1) in renal tissues of type 2 diabetes mellitus (T2DM) rats.

METHODSThe T2DM model rats induced by high sucrose/fat feeding and low dose streptozotocin injecting were randomly divided into the model group, the ZQR group, and the earthworm group. A normal control group was also set up. ZQR extract was given at the daily dose of 24 g/kg body weight by gastrogavage to rats in the ZQR group. The earthworm extract was given at the daily dose of 2.6 g/kg body weight by gastrogavage to rats in the earthworm group. Equal volume of distilled water was given to rats in the normal control group and the model group by gastrogavage. The medication was once daily for 8 successive weeks. The fasting blood glucose (FBG), serum PAI-1, 24-h urinary albumin excretion (UAE), and endogenous creatinine clearance rate (CCr) were detected. The structural changes of renal tissues stained with Periodic Acid-Schiff were observed by light microscope. The expressions of TGF-beta1 and PAI-1 were analyzed by immunohistochemistry. And the mRNA and protein expressions of TGF-beta1 and PAI-1 in the renal cortex were detected by Real-time PCR and Western blot respectively.

RESULTSCompared with the normal control group, the FBG, serum PAI-1, UAE, the mRNA and protein expressions of TGF-beta1, and PAI-1 significantly increased in the model group, and CCr obviously decreased (P<0.01). Compared with the model group, FBG, serum PAI-1, UAE obviously decreased (P<0.01) and CCr obviously increased (P<0.05) in the ZQR group. FBG was not obviously lowered in the earthworm group. The serum PAI-1 and UAE both decreased obviously (P<0.05, P<0.01) and CCr increased (P<0.05) in the earthworm group. The effects of ZQR were superior to the earthworm. The renal pathological changes got improved in the ZQR group and the earthworm group. The mRNA and protein expressions of TGF-beta1 and PAI-1 significantly decreased in the ZQR group and the earthworm group, especially in the ZQR group.

CONCLUSIONSEarly application of ZQR and earthworm in treatment of T2DM rats with nephropathy was effective in protecting the kidney. Its mechanism may possibly be correlated with inhibition of TGF-beta1 expression, resulting in down-regulation of PAI-1 expression. ZQR showed better effects than earthworm.