[Effect of ginsenoside Rgl on the expression of TNF-alpha and MCP-1 in rats with diabetic nephropathy].
OBJECTIVE
To investigate the effects of Ginsenoside Rgl on proteinuria and the expression of monocyte chemotactic protein-1 (MCP-1) and tumor necrosis factor-alpha (TNF-alpha) in rats with diabetic nephropathy (DN).


METHODS
The DN rat model was established by injection of streptozotocin (STZ, 65 mg/kg) in abdominal cavity. Forty Sprague-Dawley male rats were randomly divided into 4 groups: normal group, DN group, Ginsenoside Rgl treatment group and Irbesartan treatment group. The blood glucose was monitored routinely. Twenty-four hours urine protein and serum creatine were measured the day before the rats were killed when the eight weeks of treatments had been completed. The renal pathological and podocyte changes were evaluated. Immunohistochemistry and enzyme-linked immunosorbent assay (ELISA) were performed to examine the protein expression levels of MCP-1 and TNF-alpha, respectively. The mRNA of TNF-alpha and MCP-1 were reverse transcribed and quantified by real-time PCR.


RESULTS
The DN rats had increased volume of renal glomerulus, thickened basement membrane, and increased mesenterium mass, as well as some inflammatory cells in renal glomerulus. The number of potocyte decreased significantly in the DN group compared with the normal group (P<0.01). Compared with the DN group, the basement membrane became thinning and the number of podocyte increased in the two treatment groups (P<0.05). The rats in the DN group and the two treatment groups had significantly higher levels of twenty-four hour urine protein, serum creatine, serum glucose, serum MCP-1 and TNF-alpha than the normal rats (P<0.05). The rats in the treatment groups had lower levels of twenty-four hours urine protein and serum creatine than the rats in the DN group (P<0.05). But the serum glucose had little changes (P>0.05). There was no difference between the two treatment groups. Immunohistochemisty, ELISA and real-time PCR results indicated that the expression levels of MCP-1 and TNF-alpha in the rats in the DN group and the two treatment groups were significantly higher than those in the normal group (P<0.05). The rats in the treatment groups had lower levels of expression of MCP-1 and TNF-alpha than those in the DN group (P<0.05). The correlation analysis indicated that the levels of MCP-1 and TNF-alpha were positively related to twenty-four hours urine protein (r=0.7802, 0.6963), glomerular sclerosis index (r=0.8296, 0.7413) and thickness of podocyte membrane (r=0.7678, 0.6701, P<0.05).


CONCLUSIONS
Ginsenoside Rgl reduces the expression of MCP-1 and TNF-alpha, repairs the pathological lesions of podocyte and nephron, and reduces the twenty-four hour urine protein rats with diabetic nephropathy.
Zhang
Li-na
LN
Department of Nephrology, State Key Laboratory of Biotherapy of Human Disease, West China Hospital, Sichuan University, Chengdu 610041, China.
Xie
Xi-sheng
XS
Zuo
Chuan
C
Fan
Jun-ming
JM
D000818:Animals; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism* / Q000473:pathology; D003928:Diabetic Nephropathies / Q000378:metabolism* / Q000473:pathology; D036145:Ginsenosides / Q000494:pharmacology*; D008297:Male; D009399:Nephrons / Q000473:pathology; D005894:Panax / Q000737:chemistry; D050199:Podocytes / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013311:Streptozocin; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism*
D018932:Chemokine CCL2; D036145:Ginsenosides; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D013311:Streptozocin; C035054:ginsenoside Rg1