Objective To observe the renoprotective effects of angiotensin Ⅱ (ATⅡ) receptor antagonist, L-158809 and to explore its potential mechanisms. Methods The experimental rats consisted of normal control and type 2 diabetic model groups with or without treatment of L-158809 (2 mg?kg -1 ?d -1 ) for 16 weeks. Blood glucose, HbA 1c , serum immunoreactive insulin, serum creatinine, mean arterial blood pressure, creatinine clearance (Ccr) and urinary albumin excretion index (UAEI) as well as plasma and renal ATⅡ content were measured. The kidney morphological changes were examined by renal histopathology. Marix metalloproteinase-2 (MMP-2) and the tissue inhibitor of metalloproteinase-2 (TIMP-2) expression in renal tissues were studied by immunohistochemistry, zymography and Western blot. Results In type 2 diabetic rats, L-158809 restored the blood pressure (P

Objective To evaluate the role of tumor necrosis factor alpha-inducible protein 8 like-2 ( TIPE2) in macrophage pyroptosis in mice. Methods Mouse macrophages J774A. 1 were seeded in 6-cm culture dishes (5 ml∕dish) at the density of 2×105 cells∕ml and divided into 4 groups (n=18 each) using a random number table method: blank vector control group ( C group) , blank vector plus lipopolysaccharide ( LPS)∕ATP group ( C+LPS∕ATP group) , TIPE2 overexpression group ( T group) and TIPE2 overexpres-sion plus LPS∕ATP group ( T+LPS∕ATP group) . Cells were infected with lentivirus without TIPE2 in C and C+LPS∕ATP groups. TIPE2 overexpression stable cell line was constructed in T group and T+LPS∕ATP group. LPS 1. 0 μg∕ml was added and cells were incubated for 5 h, and then ATP 5. 0 mmol∕L was added and cells were incubated for 1 h in C+LPS∕ATP group and T+LPS∕ATP group. Cells were collected for de-tection of the expression of TIPE2, NOD-like receptor protein 3 ( NLRP3) , interleukin-1beta ( IL-1β) and interleukin-8 ( IL-18) by Western blot. Flow cytometry was used to detect the pyroptotic cells, and the per-centage of pyroptotic cells was calculated. The concentrations of tumor necrosis factor-alpha ( TNF-α) , IL-6, IL-1β and IL-18 in cell culture media were determined by enzyme-linked immunosorbent assay. Results Compared with group C, the expression of TIPE2 was significantly down-regulated, the expression of NL-RP3, IL-1β and IL-18 was up-regulated, and the percentage of pyroptotic cells and concentrations of TNF-α, IL-6, IL-1β and IL-18 in cell culture media were increased in group C+LPS∕ATP (P<0. 05). Com-pared with group T, the expression of TIPE2 was significantly down-regulated, the expression of NLRP3, IL-1βand IL-18 was up-regulated, and the percentage of pyroptotic cells and concentrations of TNF-α, IL-6, IL-1β and IL-18 in cell culture media were increased in group T+LPS∕ATP ( P<0. 05) . Compared with group C+LPS∕ATP, the expression of TIPE2 was significantly up-regulated, the expression of NLRP3, IL-1β and IL-18 was down-regulated, and the percentage of pyroptotic cells and concentrations of TNF-α, IL-6, IL-1β and IL-18 in cell culture media were decreased in group T+LPS∕ATP ( P<0. 05) . Conclusion TIPE2 can inhibit macrophage pyroptosis, and the mechanism may be related to inhibiting activation of NL-RP3 inflammasome in mice.