仙茅苷抑制ROS/NLRP3通路对主动脉夹层大鼠作用的研究OA

Objective To investigate the ameliorative effects of curculigoside on rats with aortic dissection by the inhibition of the reactive oxygen species/NOD-like receptor thermal protein domain associated protein 3(ROS/NLRP3)pathway.Methods Rats were randomly divided into control group,model group,low-dose experimental group(50 mg·kg-1 curculigoside),high-dose experimental group(100 mg·kg-1 curculigoside)and combination group(100 mg·kg-1 curculigoside and 1.75 mg·mL-1 trimethylamine N-oxide),with 12 rats in each group.The rat model of aortic dissection was established by intragastric administration of 0.1 g·kg-1β-aminopropionitrile(BAPN).Cardiac blood was collected,and the levels of interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)were determined by enzyme-linked immunosorbent assay(ELISA).hematoxylin-eosin(HE)staining and Van Gieson staining were used to evaluate histopathological changes and the degree of elastic fiber rupture.Reactive oxygen species(ROS)levels were detected using 2',7'-dichlorodihydrofluorescein diacetate(DCFH-DA)staining.The mRNA expression levels of matrix metalloproteinase 9(MMP-9)and matrix metalloproteinase 2(MMP-2)in aortic tissues were measured by quantitative real-time reverse transcription-polymerase chain reaction(qRT-PCR).The protein expression levels of apoptosis-associated speck-like protein containing a CARD(ASC),NLR family pyrin domain-containing 3(NLRP3)and caspase-1 in aortic tissues were detected by Western blotting.Results The IL-6 levels in the low-dose experimental group,high-dose experimental group,control group,model group and combination group were(49.06±4.98),(37.18±3.81),(35.62±3.63),(72.34±7.33)and(50.03±5.08)pg·mL-1,respectively;the TNF-α levels were(25.63±2.64),(16.35±1.71),(15.31±1.62),(42.06±4.23)and(26.15±2.64)pg·mL-1,respectively;the degrees of elastic fiber rupture were 2.01±0.22,0.85±0.09,0±0,3.22±0.34 and 1.85±0.19,respectively;the ROS levels were 358.62±36.64,203.11±20.15,186.34±19.11,588.64±60.03 and 361.24±37.24,respectively;the relative mRNA expression levels of MMP-9 were 1.67±0.18,1.15±0.12,1.02±0.11,2.45±0.26 and 1.72±0.19,respectively;the relative mRNA expression levels of MMP-2 were 1.88±0.19,1.24±0.14,0.98±0.10,2.85±0.30 and 1.91±0.20,respectively;the relative protein expression levels of Caspase-1 were 0.85±0.09,0.55±0.06,0.44±0.05,1.24±0.13 and 0.88±0.10,respectively;the relative protein expression levels of ASC were 0.97±0.10,0.64±0.08,0.55±0.06,1.48±0.16 and 0.89±0.09,respectively;and the relative protein expression levels of NLRP3 were 0.64±0.08,0.35±0.05,0.25±0.03,1.02±0.11 and 0.72±0.09,respectively.Compared with the control group,the above indicators in the model group were significantly different(all P＜0.05);compared with the model group,the above indicators in the high-dose experimental group were significantly different(all P＜0.05);and compared with the high-dose experimental group,the above indicators in the combination group were significantly different(all P＜0.05).Conclusion Curculigoside can effectively ameliorate BAPN-induced aortic injury in rats.Its protective mechanism against the development of aortic dissection may be associated with the inhibition of the ROS/NLRP3 signaling pathway.