Atorvastatin attenuates TNBS-induced rat colitis: the involvement of the TLR4/NF-kB signaling pathway

被引:92
|
作者
Rashidian, Amir [1 ]
Muhammadnejad, Ahad [2 ]
Dehpour, Ahmad-Reza [1 ]
Mehr, Shahram Ejtemai [1 ]
Akhavan, Maziar Mohammad [3 ]
Shirkoohi, Reza [2 ]
Chamanara, Mohsen [1 ]
Mousavi, Seyyedeh-Elaheh [1 ,4 ]
Rezayat, Seyed-Mahdi [1 ,4 ]
机构
[1] Univ Tehran Med Sci, Sch Med, Dept Pharmacol, POB 13145-784, Tehran, Iran
[2] Univ Tehran Med Sci, Canc Inst Iran, Canc Res Ctr, Tehran, Iran
[3] Shahid Beheshti Univ Med Sci, Skin Res Ctr, Tehran, Iran
[4] Islamic Azad Univ IAUPS, Sch Pharm, Pharmaceut Sci Branch, Dept Pharmacol & Toxicol, Tehran, Iran
关键词
Atorvastatin; Ulcerative colitis; TNBS; TLR4/NF-kappa B signaling pathway; TOLL-LIKE RECEPTORS; INFLAMMATORY-BOWEL-DISEASE; SODIUM-INDUCED COLITIS; NF-KAPPA-B; REDUCTASE INHIBITOR; ULCERATIVE-COLITIS; MURINE COLITIS; EXPRESSION; MICE; RECOGNITION;
D O I
10.1007/s10787-016-0263-6
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The aim of the present study is to explore whether atorvastatin improves intestinal inflammation through the inhibition of the TLR4/NFkB signaling pathway in TNBS-induced rat colitis. Acute colitis was induced by intra-rectal administration of 100 mg/kg TNBS dissolved in 0.25 ml of 50 % ethanol. Twenty four hours after colitis induction, saline, atorvastatin (20 and 40 mg/kg) and sulfasalazine (100 mg/kg) were given to the animals by oral route. This was repeated daily for 1 week. Body weight changes, macroscopic and microscopic lesions were assessed. MPO and TNF-alpha activities were detected by immunohistochemistry (IHC) and the expression level of TLR4, MyD88 and NF-kappa B p65 proteins were measured by western blotting analysis. Atorvastatin and sulfasalazine reduced the body weight loss, macroscopic and microscopic lesions. Additionally, both drugs decreased the expression of MPO and TNF-alpha positive cells in the colon tissue. Furthermore, they inhibited the TNBS-induced expression of TLR4, MyD88 and NF-kappa B p65 proteins. It is suggested that the anti-inflammatory effect of atorvastatin on TNBS-induced rat colitis may involve the inhibition of the TLR4/NFkB signaling pathway.
引用
收藏
页码:109 / 118
页数:10
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