Objective: To investigate the protective effect of angiotensin Ⅱ receptor blocker (ARB) irbesartan on myocardial inflammation in db/db mice with type 2 diabetes and its cardioprotective mechanism.
Methods: 10-week-old db/db mice were randomly divided into model group and irbesartan treatment group at 50 mg/(kg·d), and 10-week-old non-diabetic db/+ mice born in the same littermate served as normal control group. The normal group and the model group were given an equal volume of normal saline, and the irbesartan treatment group was given irbesartan (dissolved in normal saline). The contents of triesters and blood total cholesterol were detected by HE staining, Western blot, immunohistochemistry and qPCR in the heart.
Results: Compared with the normal group db/+ mice, the model group db/db mice developed obesity, hyperglycemia and hyperlipidemia (P<0.01); myocardial fibers were disordered, interstitial increased, and inflammatory cell infiltration; P -IкBα protein level increased, IкBα protein level decreased, P-IкBα/IкBα increased (P<0.001); NF-кB (P65) activity increased, nuclear entry increased (P<0.001), and pro-inflammatory cytokines interleukin The mRNA levels of IL-6 (IL-6) and tumor necrosis factor α (TNF-α) were increased (P<0.01), and these abnormalities were related to the increased inflammatory response of diabetic myocardial tissue. Chronic treatment with irbesartan ameliorated myocardial pathological changes and improved hyperglycemia-induced myocardial tissue inflammatory response indicators in type 2 diabetic db/db mice.
Conclusion: Irbesartan improves myocardial tissue inflammation in type 2 diabetic db/db mice, and its mechanism may be related to the inhibition of cardiac angiotensin II and NF-κB signaling pathway.