右美托咪定对脂多糖诱导的脓毒症大鼠全身炎症反应和肺损伤的影响

Pulmonary protective effects of dexmedetomidine in septic rats induced by LPS

目的观察脂多糖(LPS)对大鼠血浆和肺组织中的炎性因子和Toll样受体4(TLR4)表达的影响及右美托咪定的干预作用。方法雄性SD大鼠40只,250~300g,随机分为四组。Control组(n=10)生理盐水1ml·kg^(-1)·h^(-1)大鼠尾静脉泵注6h;DEX组(n=10)右美托咪定(负荷量6.5μg·kg^(-1)·h^(-1),10min;5μg·kg^(-1)·h^(-1)维持)大鼠尾静脉泵注6h;LPS组(n=10)经大鼠尾静脉注射7.5mg/kg的LPS后继续生理盐水泵注6h;LPS+DEX组(n=10)经大鼠尾静脉注射7.5mg/kg的LPS后泵注右美托咪定6h。以6h为实验终结点,并于此时行右心室取血和肺组织标本的制备。采用ELISA法检测血浆IL-1、IL-6、TNF-α浓度,Western blot法检测肺组织TLR4、髓样分化因子88(MyD88)、NF-κB蛋白含量;检测大鼠肺组织湿/干比(W/D);并用Murakami法评测肺损伤程度。结果与Control组比较,LPS组大鼠血浆IL-1、IL-6和TNF-α浓度明显升高,肺组织中的TLR4、MyD88、NF-κB蛋白含量明显升高(P<0.01),肺W/D明显升高;LPS+DEX组上述指标差异均无统计学意义。Control组和DEX组未见明显肺损伤,LPS组肺间质水肿、炎性细胞浸润明显,LPS+DEX组肺损伤程度明显减轻(P<0.01)。结论 LPS的刺激可以明显升高大鼠血浆中炎性因子以及肺组织中TLR4的表达水平,右美托咪定的干预可以减轻这一趋势,缓解大鼠的全身炎症和肺水肿的程度。

Objective To assess the role of intervention of dexmedetomidine in lung tissue and plasma of septic rats induced by lipolysaccharide.Methods Forty SD rats weighing 250-300 g were divided into 4groups：control group（n=10）with saline（1 ml·kg^-1·h^-1）infused through the tail veins of rats for 6h;dexmedetomidine（DEX）group（n=10）with dexmedetomidine,injected 6.5μg·kg^-1·h^-1 for 10 min followed by 5μg·kg^-1·h^-1,continuously infused through tail veins for 6h;lipolysaccharide（LPS）group（n=10）with lipolysaccharide（7.5 mg/kg）infused through the tail veins of rats;LPS＋DEX group（n=10）,after infusion of LPS,rats were treated with dexmedetomidine（bolus 6.5μg·kg^-1·h^-1,10min;5μg·kg^-1·h^-1,continuous infusion）through the tail veins for 6h.ELISA and Western blot were performed to assess the protein expression of IL-1,IL-6,TNF-αand TLR4;the wet/dry ratio（W/D）of lung tissue in each group was measured and the injury scores were recorded through the Murakami method.Results There was no statistical significance between the control group and DEX group in plasma level of inflammatory factors,pulmonary TLR4 expression,wet/dry ratio and injury score of lung tissues,however,compared to the control group,there was a significant elevation in the above-mentioned biomarkers,W/D and injury score of lung tissue（P〈0.01）.Compared to the control group,there was no statistical significance in the LPS＋DEX group.Compared to the LPS＋DEX group,the biomarkers mentioned above,W/D and injury score of lung tissues were significantly elevated in the LPS group（P〈0.01）.Conclusion The irritation of LPS can trigger the elevation of inflammatory factors in plasma,TLR4 expression in lung tissues in rats,while the intervention of dexmedetomidine can significantly alleviate this tendency.Dexmedetomidine can suppress the inflammatory reaction and pulmonary edema in septic rats.