Role of Cannabinoid Type 2 Receptor Activation in Renal Fibrosis Induced by Unilateral Ureteric Obstruction in Rats

大麻素 2 型受体激活在大鼠单侧输尿管梗阻诱发的肾脏纤维化中的作用

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作者:Mahmoud El Tohamy, Mohamed Adel, Fayza Rashad El-Menabawy, Gad El Mawla Gad, Randa El-Gamal, Hanaa El Serougy

Background

Chronic kidney disease (CKD) ends mostly with renal fibrosis. The effect of CB2 receptor on renal fibrosis has been unclear. The

Conclusions

The improvement of these parameters with JWH-133 suggests an anti-fibrotic role of CB2 receptor activation through reduction of oxidative stress, apoptosis, and autophagy.

Methods

50 adult male Sprague-Dawley rats were divided into 5 groups; normal, sham; rats had their ureters only manipulated, UUO; rats had their left ureters ligated, and JWH post; rats had their left ureters ligated and they received JWH 133 for 14 days, JWH pre+post; rats received JWH 133 for 14 days before and after UUO procedure. Serum creatinine and BUN were assessed together with tissue MDA, GSH, and catalase. Histopathological evaluation of the renal tissue by H&E and Masson's trichrome was done. Immunohistochemical staining for TGF-β1, AQP1, Caspase-3, LC3B and p62 was performed. AQP1 and CB2 receptors genes expression was detected by quantitative RT-PCR.

Results

UUO had caused severe damage in the renal tissue with reduction of the renal function parameter accompanied by increase in the collagen deposition with increase TGF-β1 and decrease AQP1 expression. Conclusions: The improvement of these parameters with JWH-133 suggests an anti-fibrotic role of CB2 receptor activation through reduction of oxidative stress, apoptosis, and autophagy.

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