Effects of total glucosides of paeony on immune regulatory toll-like receptors TLR2 and 4 in the kidney from diabetic rats.
TLRs are a family of receptors that play a critical role in the pathogenesis of diabetic nephropathy. TGP have been shown to have anti-inflammatory and immuno-regulatory activities. However, the relation between TGP and TLRs on diabetic nephropathy remains unknown. In this study, we examined effects of TGP on immune regulatory TLR2 and 4 in the kidney from streptozotocin-induced diabetic rats. TGP decreased the levels of 24h urinary albumin excretion rate significantly in diabetic rats. Western blot analysis showed that TGP significantly inhibited the expression of TLR2 and 4, MyD88, p-IRAK1, NF-κB p65, p-IRF3, TNF-α and IL-1β. Quantitative real-time PCR analysis showed that the significantly increased levels of TLR2 and 4, and MyD88mRNA in the kidneys of diabetic rats were significantly suppressed by TGP treatment. Macrophages infiltration were also markedly increased in the kidneys of the diabetic rats, but were significantly inhibited by TGP in a dose-dependent manner. These results suggest that TGP has protective effects on several pharmacological targets in the progress of diabetic nephropathy by selectively blocking TLRs activation in vivo.
Department of Nephrology, the First Affiliated Hospital, Anhui Medical University, Hefei, Anhui, PR China.
Xing-xin
XX
Xu
Department of Nephrology, the First Affiliated Hospital, Anhui Medical University, Hefei, Anhui, PR China.
Xiang-Ming
XM
Qi
Department of Nephrology, the First Affiliated Hospital, Anhui Medical University, Hefei, Anhui, PR China.
Wei
W
Zhang
Department of Nephrology, the First Affiliated Hospital, Anhui Medical University, Hefei, Anhui, PR China.
Chao-Qun
CQ
Zhang
Department of Nephrology, the First Affiliated Hospital, Anhui Medical University, Hefei, Anhui, PR China.
Xiao-Xu
XX
Wu
Department of Nephrology, the First Affiliated Hospital, Anhui Medical University, Hefei, Anhui, PR China. Electronic address: wuyonggui@medmail.com.cn.
Yong-Gui
YG
Wu
Department of Nephrology, the First Affiliated Hospital, Anhui Medical University, Hefei, Anhui, PR China.
Kun
K
Wang
Department of Pathobiology, Anhui Medical University, Hefei, Anhui, PR China.
Ji-Jia
JJ
Shen
D000418:Albumins / Q000378:metabolism; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000188:drug therapy; D003928:Diabetic Nephropathies / Q000188:drug therapy* / Q000378:metabolism; D005960:Glucosides / Q000494:pharmacology / Q000627:therapeutic use*; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects; D008297:Male; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics / Q000378:metabolism; D029596:Paeonia / Q000737:chemistry*; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use; D012333:RNA, Messenger / Q000378:metabolism; D017208:Rats, Wistar; D051195:Toll-Like Receptor 2 / Q000378:metabolism*; D051197:Toll-Like Receptor 4 / Q000378:metabolism*
D000418:Albumins; D005960:Glucosides; D053594:Myeloid Differentiation Factor 88; D010936:Plant Extracts; D012333:RNA, Messenger; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4
Diabetic nephropathy; Inflammation; NF-κB; Toll-like receptors; Total glucosides of paeony