Combined MMF and insulin therapy prevents renal injury in experimental diabetic rats.
Conventional therapies for diabetic mellitus are not effective in preventing the progression from early diabetic nephropathy (DN) to end-stage renal disease. The role of inflammation in the pathogenesis of DN has been implicated both clinically and experimentally, which provides an alternative therapeutic target for DN. Anti-inflammatory impact of mycophenolate mofetil (MMF) alone and in combination with insulin had been observed in a rat model of experimental DN. In this study, the diabetic rats were subjected to different treatments. Compared to control, the expression levels of CD68, NGF, and NF-kappaB p65, as determined immunohistochemically, were elevated in diabetic rats. Treatment with combined MMF/insulin is associated with a significant reduction in renal tissue of NGF and NF-kappaB p65 expression, macrophage infiltration. It also partially improved the renal function and attenuated renal hypertrophy at early stage of DN. CD68 was found to positively correlate with urinary albumin excretion and NGF. The combined use of MMF/insulin seemed to offer more protections in rats with experimental diabetic renal injury, and the protective effects of MMF might be due to its anti-inflammatory actions through inhibition of NF-kappaB activation and reduction of T cells and macrophage infiltration and/or other kidney chemokine productions.
Wu
Xiaoyan
X
Division of Nephrology, Zhongnan Hospital, Wuhan University, Wuhan, Hubei 430071, People's Republic of China.
Zha
Dongqing
D
Xiang
Guangsheng
G
Zhang
Bo
B
Xiao
Shu-Yuan
SY
Jia
Ruhan
R
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000473:pathology; D003928:Diabetic Nephropathies / Q000188:drug therapy* / Q000473:pathology; D004359:Drug Therapy, Combination; D005260:Female; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D049528:Insulin, Long-Acting / Q000627:therapeutic use*; D007668:Kidney / Q000473:pathology*; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar
D000894:Anti-Inflammatory Agents, Non-Steroidal; D007004:Hypoglycemic Agents; D049528:Insulin, Long-Acting; D009173:Mycophenolic Acid