Trpc6敲除抑制炎症小体减轻小鼠心肌炎症损伤的作用OA

Objective To investigate the effects of Trpc6 knockout on chronic lipopolysaccharide(LPS)-induced myocardial inflammation and fibrosis in mice and its potential mechanisms.Methods Male C57BL/6 wild-type(WT)mice and Trpc6 knockout(Trpc6-/-)mice of the same background were randomly divided into four groups:WT control,WT+LPS(200 μg/kg),Trpc6-/-control,and Trpc6-/-+LPS(200 μg/kg).Group with LPS received in-traperitoneal LPS injections for 21 consecutive days to induce chronic myocardial inflammatory injury.Cardiac ul-trasound assessed changes in left ventricular ejection fraction(EF),left ventricular shortening fraction(FS),and cardiac output(CO).Hematoxylin and eosin(HE)staining and periodic acid-Schiff(PAS)staining were used to examine morphological alterations in myocardial tissue.Masson's trichrome staining was used to assess myocardial fiber alterations;Western blot analysis was used to measure myocardial tissue expression of transient receptor po-tential calcium channel 6(TRPC6),NOD-like receptor family pyrin domain-containing 3 inflammasome(NLRP3),absent in melanoma 2 inflammasome(AIM2),Caspase-1,interleukin(IL)-6,and IL-1β in mouse myocardial tissue.Results Compared with the WT control group,the WT+LPS group exhibited decreased cardiac EF(P<0.01),FS(P<0.01),and CO(P<0.05),along with significantly increased myocardial tissue damage,glycoprotein deposition,and fibrosis(P<0.01).Further analysis revealed that compared with the WT control group,the WT+LPS group exhibited markedly increased myocardial tissue expression of TRPC6,NLRP3,AIM2,Caspase-1,IL-6,and IL-1β(P<0.01).Compared with the WT+LPS group,mice in the Trpc6-/-+LPS group ex-hibited elevated EF(P<0.01)and FS(P<0.05),along with reduced myocardial tissue injury,glycoprotein depo-sition,and fibrosis(P<0.05).Conclusion Chronic LPS treatment can activate NLRP3/AIM2 inflammasomes through the up-regulation of TRPC6 expression,and then lead to chronic myocardial inflammatory injury and fibro-sis,while Trpc6 knockdown can reduce myocardial inflammatory injury and fibrosis,and the mechanism is related to inhibiting the activation of NLRP3/AIM2 inflammasomes.