Regulation Of Total Glucosides Of Paeony On Local Macrophage Proliferation And STAT3 Activation In The Kidney From Diabetic Rats

Background and objective Diabetic nephropathy is a serious microvascular complication of diabetes mellitus and the major cause of end-stage renal disease, as its incidence has increased year by year. In the last few years, activation of immune response and inflammation has been known are part of the mechanisms which cause organism injury in diabetes. And current evidence supports a critical role for macrophages in the evolution of diabetic complications. Therefore, inhibition of immune response and inflammation, especially blockade of macrophage accumulation and function may become a key therapeutic strategy for preventing the development of diabetes complications. Non-activated macrophages have no injury effect, only activating macrophages can be cells which have active biological function. The STAT3 is an important member which is associated with inflammation and cell proliferation. Total glucosides of paeony (TGP) was the traditional Chinese herbal medicine in our country, its pharmacological effect is anti-inflammation, antioxidant and regulation of the immune. In the present study, we investigate the regulation of total glucosides of paeony (TGP) on local macrophage proliferation and STAT3 activation in the kidney from diabetic rats and explore its possible renoprotection mechanisms.Methods Fifty adult male Sprague-Dawley rats were separated into five groups at random. Control group (n=10), model group (n=10), model group treated with TGP (50 mg·kg^-1d^-1, n=10), model group treated with (TGP100 mg·kg^-1d^-1, n=10) and model group treated with TGP (200 mg·kg^-1d^-1, n=10). Diabetes was induced with streptozotocin (65 mg·kg^-1d^-1) in rats, and TGP was orally administered once a day for 8wk to rats. Eight weeks after STZ injection, the following determinations were done in samples: 1.BG were determined according to standard methods; 2. Urinary albumin excretion rate was measured by enzyme immunoassay (EIA); 3. ED-1 positive cells; PCNA and ED-1 double positive cells; p-STAT3 and ED-1 double positive cells were measured with immunohistochemistry and double immunohistochemistry immunostaining in the kidney.Results Elevated 24h urinary albumin excretion was markedly attenuated by TGP treatment with 50, 100 and 200 mg·kg^-1d^-1 in diabetic rats. There were marked accumulation and proliferation of macrophage in diabetic kidney (P<0.01), which were significantly inhibited by treatment with TGP (P<0.01). P-STAT3 positive cells in diabetic kidney group were significantly increased when compared with the values in control rats (P<0.01). Elevated p-STAT3 positive cells was significantly attenuated by TGP treatment with 50, 100 and 200 mg·kg^-1 (P<0.05, 0.01). ED-1 and p-STAT3 double positive cells were significantly increased in kidneys from model group, while they were significantly inhibited by TGP treatment (P<0.01).Conclusion Our data suggest that TGP treatment ameliorates early renal injury via the inhibition of macrophage infiltration, proliferation and STAT3 activation in the kidneys from diabetic rats.