[Protective effects and mechanisms of xin'ganbao capsule on STZ induced early kidney injury in diabetic rats].
OBJECTIVE
To discuss the protective effects of Xin'ganbao Capsule (XC) on early kidney injury in streptozocin (STZ)-induced diabetic rats and its mechanisms.


METHODS
Twenty-four male Wistar rats were selected to establish STZ induced diabetes mellitus (DM) model. After modeling they were randomly divided into the model group,the XC group (at the daily dose of 0.5 g/kg), and the benazepril group (at the daily dose of 4 mg/kg), 8 in each group. Another 8 rats were chosen as the blank control group. Rats in the model group and the blank control group were administered with equal volume of normal saline by gastrogavage for 8 successive weeks. The blood glucose was monitored by the end of the 4th week and the 8th week. The 24 h urine protein (24 hUP), blood urea nitrogen (BUN), and serum creatinine (SCr) were detected by the end of the 8th week. The transforming growth factor-beta1 (TGF-beta1), laminin (LN), collagen IV (Col-IV) expression were detected using immunohistochemical assay. The mRNA expressions of renal TGF-beta1, tissue inhibitor of matrix metalloproteinase-1 (TIMP-1), and plasminogen activator inhibitor-1 (PAI-1) were detected using RT-PCR. The pathological changes of the renal tissue were observed by HE, PAS, and Masson stain methods.


RESULTS
Compared with the blank control group, hyperglycemia, polydipsia, polyphagia, polyuria, weight loss, emaciation, dry and dim body hair, and irritability appeared in the diabetic rats. After 8 weeks the symptoms of the two medication groups were attenuated. When compared with the blank control group, the 24 hUP, SCr, blood glucose, Col-IV, LN, TGF-beta1 positive expression ratio, the levels of TGF-beta1, TIMP-1, PAI-1 mRNA, the area of glomerular (GA), extracellular matrix (ECM), and ECM/GA all increased in the model group with statistical difference (P<0.01). The pathological changes showed obvious glomerular enlargement, the capillary loop expansion, the proliferation of the mesangial cells, increased mesangial matrix, widen and thicken glomerular basement membrane (GBM), and tubular derangement. The vacuolar degeneration and shedding could be seen in partial epithelial cells. The protein cast could also be seen with infiltration of interstitial inflammatory cells. Compared with the model group, each index of the two medication groups decreased with statistical difference (P<0.01). The pathological changes were less in the two medication groups. The mesangial cells were slightly proliferated and the mesangial matrix slightly increased. The mRNA expressions of SCr and PAI-1 were lower in the XC group than in the benazepril group (P<0.05). There was no statistical difference in the other indices between the two medication groups (P > 0.05). Conclusions XC had some protective effects and anti-glomerulosclerosis effects on early kidney injury in STZ-induced diabetic rats. Its mechanisms might be associated with down-regulating the mRNA expressions of TGF-beta1, TIMP-1, PAI-1, and Col-IV, reducing ECM and urine protein.
Department of Nephrology, Qilu Hospital of Shandong University, Jinan 250012.
Jie
J
Gao
Li
L
Fan
Mao-Jing
MJ
Liu
D000818:Animals; D001552:Benzazepines / Q000627:therapeutic use; D024141:Collagen Type IV / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D004365:Drugs, Chinese Herbal / Q000494:pharmacology / Q000627:therapeutic use*; D005109:Extracellular Matrix / Q000378:metabolism; D007668:Kidney / Q000473:pathology; D007797:Laminin / Q000378:metabolism; D008297:Male; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
D001552:Benzazepines; D024141:Collagen Type IV; D004365:Drugs, Chinese Herbal; D007797:Laminin; D017395:Plasminogen Activator Inhibitor 1; C576839:TIMP1 protein, rat; C508962:Tgfb1 protein, rat; D019715:Tissue Inhibitor of Metalloproteinase-1; D053773:Transforming Growth Factor beta1; C044946:benazepril