硫辛酸在急性百草枯中毒致心肌损伤中保护作用的实验研究

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目的:观察抗氧化剂硫辛酸对急性百草枯中毒造成的心肌损伤,心肌组织中NF-κB、NOS、NO及血中心肌酶谱的变化的影响,探讨硫辛酸对百草枯中毒所致心肌损伤的可能保护机制。方法:选择健康雄性Sprage-Dawley大鼠126只,随机分4组:正常对照组(NS)、百草枯中毒组(PQ)、百草枯+还原型谷胱甘肽组(GSH)、百草枯+硫辛酸治疗组(LA)。NS组6只;PQ组和GSH组各24只;LA组72只,再细分3个亚组,即30mg/kg、60mg/kg、100mg/kg亚组,每亚组24只。NS组给予生理盐水灌胃;PQ组给予PQ 50mg/kg灌胃;GSH组给予PQ 50mg/kg灌胃,半小时后给予GSH 200mg/kg/d腹腔注射,连续6d;LA组给予PQ 50mg/kg灌胃半小时后分亚组给予LA 30mg/kg/d、60mg/kg/d、100mg/kg/d腹腔注射,连续6d。于造模成功后1d、3d、5d、7d取大鼠相同部位的心肌组织HE染色,光镜下观察组织学变化;取另外相同部位心肌组织检测NF-κB、NOS、NO水平;腹主动脉取血检测AST、LDH、CK、CKMB水平。结果:①HE染色结果显示PQ组心肌破坏严重,心肌组织严重水肿,出血,点状坏死灶,组织间隙增宽,心肌细胞广泛肿胀、变性。GSH组在进行干预后出现上述情况较同时点的PQ组减轻。LA组在进行干预后出现上述情况较同时点的PQ组及GSH组少,心肌组织损伤轻,主要表现为局部嗜酸性变。随着LA剂量的增加,效果更加显著。②NF-κB水平、NOS的活力、NO水平:LA组与PQ组、GSH组的各相同时点对比均低,P<0.01有统计学意义;LA组各时点与NS组对比均高,P<0.05有统计学意义;随着LA剂量的增加,NF-κB水平、NOS的活力、NO水平进行性下降,各组间比,P<0.05有统计学意义。③AST、LDH、CK、CKMB水平:LA组与PQ组、GSH组的各相同时点对比均低,P<0.01有统计学意义;LA组各时点与NS组对比均高,P<0.05有统计学意义;随着LA剂量的增加,AST、LDH、CK、CKMB水平进行性下降,各组间比,P<0.05有统计学意义。结论:硫辛酸在急性百草枯中毒中能使心肌组织的损伤减轻,其机制可能是通过直接调控NF-κB、NOS、NO的水平,影响心肌组织中自由基和炎症介质的含量,从而减轻心肌水肿、出血和坏死,改善心肌细胞代谢,保护心肌组织。 OBJECTIVE: To observe the effects of lipoic acid on myocardial injury caused by acute paraquat poisoning, changes of NF-κB, NOS, NO and myocardial enzymes in myocardial tissue, and to explore the possible effect of lipoic acid on myocardial injury induced by paraquat poisoning protection mechanism. Methods: 126 healthy male Sprague-Dawley rats were randomly divided into 4 groups: normal control group (NS), paraquat poisoning group (PQ), paraquat + GSH group, paraquat + Lipoic acid treatment group (LA). 6 in NS group, 24 in PQ group and GSH group, 72 in LA group and subdivided into 3 subgroups, 30mg / kg, 60mg / kg, 100mg / kg subgroup, 24 in each subgroup. The rats in NS group received intragastric administration of physiological saline; PQ group received 50 mg / kg PQ orally; GSH group received PQ 50 mg / kg orally; GSH 200 mg / kg / d was intraperitoneally injected for half an hour for 6 consecutive days; kg intragastric administration of 30 mg / kg / d, 60 mg / kg / d and 100 mg / kg / d ip for 6 days. The rats in the same site were stained with HE at 1d, 3d, 5d and 7d after successful modeling, histological changes were observed under light microscope. The myocardial tissue with the same location was used to detect the levels of NF-κB, NOS and NO. The abdominal aorta Blood test AST, LDH, CK, CKMB levels. Results: ①The results of HE staining showed that myocardial damage was serious in PQ group, myocardial edema, hemorrhage, punctate necrosis, widened interstitial space and extensive swelling and degeneration of myocardial cells. In the GSH group, the above situation was alleviated compared with the PQ group at the same time after the intervention. Compared with the PQ group and the GSH group, the LA group had less myocardial damage after the intervention, which mainly manifested as local eosinophilic changes. With the LA dose increase, the effect is more significant. ②NF-κB level, NOS activity and NO level in LA group were significantly lower than those in PQ group and GSH group (P <0.01) <0.05 was statistically significant. With the increase of LA dose, the levels of NF-κB, NOS activity and NO decreased progressively. There was significant difference between each group (P <0.05). ③The levels of AST, LDH, CK and CKMB in the LA group were significantly lower than those in the PQ group and the GSH group at each same time point, P <0.01 was statistically significant; Statistical significance; With the increase of LA dose, the levels of AST, LDH, CK and CKMB decreased progressively, and there was significant difference between groups (P <0.05). CONCLUSION: Lipoic acid can attenuate myocardial injury in acute paraquat poisoning. The possible mechanism is that lipoic acid may decrease the content of free radicals and inflammatory mediators in myocardium by directly regulating the levels of NF-κB, NOS and NO, Edema, hemorrhage and necrosis, improve myocardial cell metabolism, protect myocardial tissue.
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