| BackgroundAflatoxin B1(AFB1)is a mycotoxin produced by Aspergillus flavus and Aspergillus parasiticus.The human health problems secondary to its dietary intake have attracted widespread attention.At present,the study of AFB1 induced tissue damage is mostly limited to the liver,but the mechanism of its induced myocardial toxicity is relatively less.It has been pointed out that the myocardial injury induced by AFB1 is related to the inflammatory response.The intiation of inflammation usually requires sensors,such as NLRP3(NOD like receptor protein 3)inflammasome.However,the overactivation of NLRP3 inflammasome is the core event of many diseases.Moreover,liver is the the main target of AFB1,and its injury is reported to be related to the activition of NLRP3 inflammasome.AimIn this study,by detecting the expression of NLRP3 and other important components of the inflammasome and the effect of mcc950(a selective NLRP3 inflammasome inhibitor)on the degree of myocardial injury in AFB1 induced rat myocardial injury model,the role of NLRP3 inflammsome in the pathogenesis of AFB1-induced myocardial toxicity were explored.MethodPart 1: The rats were randomly divided into control group,low exposure AFB1 group and high exposure AFB1 group.Every group contained 5 rats.The rats in the low-dose and high-dose groups were given AFB1 solution at the doses of 0.15 mg / kg and 0.3 mg / kg by gavage once a day for 6 weeks,respectively,while rats in controls received the same amount of vehicle only.In this study,hematoxylin-eosin staining HE was used to observe the morphological changes of myocardium.And the expression of NLRP3,ASC,caspase-1p20 and IL-1β protein in heart was assayed by Western blot and ELISA.Part 2: The rats were randomly divided into three groups(5 animals/group): control group,AFB1 group and AFB1+MCC950 group.The rats in the AFB1 group and AFB1+MCC950 group were given AFB1 solution(0.3 mg / kg.D)by intragastric administration once a day for 6 weeks;in addition,rats in the AFB1 + MCC950 group were intraperitoneally injected with MCC950(a selective NLRP3 inflammasome inhibitor)in the doses of 10 mg/kg.d,three times a week for 6 weeks.Blood was then collected from the abdominal aorta and the levels of lactate dehydrogenase(LDH)and creatine kinase-MB(CK-MB)in serum of the three groups were compared.Result1.Histological score in heart: after exposure to different concentrations of AFB1,different degrees of histomorphological changes can be observed.Both doses of AFB1(0.15 and 0.3 mg/kg)increased pathological score of the hearts,but there was a significant difference only in the high-dose AFB1 treatment group when compared with the control group(P < 0.05).2.The alterated expression of proteins in heart tissue samples: the results showed that the heart treated with different concentration had different expression of NLRP3 and other important components of the inflammasome.The expression of NLRP3 and ASC in the high dose group was significantly higher than that in the control group(P < 0.01).Compared with control group and the high dose group,there was no statistically significant difference in the expression of NLRP3 and ASC in the low dose group(P > 0.05).Compared with the control group,there were statistically significant differences in the expression of caspase-1p20 and IL-1β after AFB1 treatment with different concentrations(P<0.05).3.The contents of LDH and CK-MB in serum: The values of LDH and CK-MB in AFB1 group were significantly higher than those in the control group;moreover,the values of LDH and CK-MB in AFB1 + MCC950 group reduced compared with the AFB1 group(P <0.05).Conclusion1.With acute myocardial injury of rat induced by AFB1,expression of NLRP3 and other important components of the inflammasome on myocardium tissue of rats was increased,and the increase of the dose of AFB1,the more expression of them,showing a certain dose effect trend.2.NLRP3 inhibitor(MCC950)treatment could effectively improve the myocardial injury induced by AFB1 in rats. |
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