新斯的明对百草枯中毒大鼠全身炎症反应和肺损伤的影响

来源 :第三军医大学学报 | 被引量 : 0次 | 上传用户:runzhong
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目的观察胆碱酯酶抑制剂——新斯的明对百草枯中毒大鼠全身炎症反应和肺损伤的影响。方法 96只SD大鼠随机分为3组(n=32)。NES组:腹腔注射百草枯(paraquat,PQ)溶液20 mg/kg后2 h腹腔注射新斯的明300μg/kg;PQ组:腹腔注射等量PQ溶液后2 h腹腔注射生理盐水300μg/kg;对照组:以等量生理盐水代替PQ溶液腹腔注射。在6、24、72 h 3个时间点观察大鼠血清及肺组织TNF-α、IL-6、IL-10变化;分批处死大鼠进行肺组织病理学观察以及测量肺湿/干质量(W/D);Real-Time PCR检测肺组织SOCS1、SOCS3 mRNA表达。结果 PQ染毒后,大鼠血清和肺组织TNF-α、IL-6、IL-10均显著升高,NES组在染毒后各时间点血清和肺组织TNF-α水平低于PQ组(P<0.05),在染毒后24、72 h血清及肺组织IL-6水平低于PQ组(P<0.05)。染毒后各时间点NES组IL-10水平高于PQ组(P<0.05)。染毒后72 h,病理学观察可见NES组大鼠肺损伤程度较PQ组轻。NES组24、72 h肺湿干质量比低于PQ组(P<0.05)。PQ染毒后各时间点SOCS1、SOCS3 mRNA表达水平高于对照组(P<0.05)。NES组SOCS3 mRNA表达水平高于PQ组,但SOCS1 mRNA表达水平与PQ组差异无统计学意义(P>0.05)。结论新斯的明能减轻PQ中毒大鼠的全身炎症反应和肺损伤程度,其机制可能涉及激活胆碱能抗炎途径 Objective To investigate the effects of cholinesterase inhibitor neostigmine on systemic inflammatory response and lung injury in paraquat poisoning rats. Methods 96 SD rats were randomly divided into three groups (n = 32). NES group: intraperitoneal injection of neostigmine 300 μg / kg 2 h after intraperitoneal injection of paraquat (PQ) solution 20 mg / kg; PQ group: intraperitoneal injection of saline 300 μg / kg 2 h after intraperitoneal injection of equal amount of PQ solution; Control group: the same amount of saline instead of PQ solution intraperitoneal injection. The changes of TNF-α, IL-6 and IL-10 in serum and lung tissue were observed at 6, 24 and 72 h. Rats in each group were sacrificed to observe the pathological changes of lung tissue and the lung wet / dry mass W / D). Real-time PCR was used to detect the mRNA expression of SOCS1 and SOCS3 in lung tissue. Results The levels of TNF-α, IL-6 and IL-10 in serum and lung tissue were significantly increased after PQ exposure in rats. The level of TNF-α in serum and lung tissue of NES group was lower than that of PQ group P <0.05). IL-6 levels in serum and lung tissue were lower than those in PQ group 24 and 72 h after exposure (P <0.05). The level of IL-10 in NES group was higher than that in PQ group at each time point (P <0.05). 72 h after exposure, pathological observation showed that the degree of lung injury in NES rats was lighter than that in PQ rats. The wet and dry weight ratio of lung in the NES group was lower than that in the PQ group at 24 and 72 h (P <0.05). The expression of SOCS1 and SOCS3 mRNA at each time point after PQ exposure were higher than those in control group (P <0.05). The expression of SOCS3 mRNA in NES group was higher than that in PQ group, but there was no significant difference between SOCS1 mRNA and PQ group (P> 0.05). Conclusion Neostigmine can reduce systemic inflammatory response and lung injury in rats with PQ poisoning, and its mechanism may involve the activation of cholinergic anti-inflammatory pathway
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