氯胺酮预处理对谷氨酸诱发大鼠肺损伤的保护作用

目的:观察不同剂量氯胺酮预处理对谷氨酸诱发大鼠肺损伤的保护作用及其机制。方法:50只成年雌性SD大鼠,随机分为5组:空白对照组(S组);对照组(C组),采用0.75 mg/kg谷氨酸静脉注射诱发肺损伤;氯胺酮低、中、高剂量组(K5、K10、K50组),分别以氯胺酮5 mg/kg、10 mg/kg、50 mg/kg腹腔内注射预处理20 min后再静脉注射0.75 mg/kg谷氨酸。测定各组肺组织湿/干质量比值(W/D比值);逆转录聚合酶链反应(RT-PCR)法测定肺组织中肿瘤坏死因子-α(TNF-α)mRNA含量;蛋白印迹法(Western blot)法测定肺组织中核因子-κB(NF-κb/P65)含量;比较各组肺组织HE染色后病理评分。结果:(1)W/D比值:S组显著低于其他各组,K5和C组间无显著差异,K10和K50组较K5和C组显著降低(P<0.05),K50组较K10组显著降低(P<0.05);(2)肺组织中TNF-αmRNA含量:S组(0.87±0.85)显著低于C组(2.49±0.39)和K5组(1.96±0.66)(P<0.05)。K10组(1.59±0.57)和K50组(1.04±0.39)显著低于K5组和C组(P<0.05),K50组显著低于K10组(P<0.05)。NF-κb/P65含量:S组(0.11±0.15)pg/mL显著低于C组(0.87±0.15)pg/mL、K5组(0.64±0.25)mg/mL和K10组(0.39±0.14)pg/mL(P<0.05)。K5、K10、K50组显著低于C组(P<0.05)。K10组和K50组(0.26±0.10)pg/mL显著低于K5组(P<0.05);(3)病理评分:S组显著低于各组。K5组和C组间无显著差异,K10组和K50组显著低于K5和C组(P<0.05),K50组显著低于K10组(P<0.05)。TNF-αmRNA与NF-κb/P65呈正相关(r=0.64,P<0.05)。结论:氯胺酮预处理对大鼠谷氨酸诱发的肺损伤有保护作用,且其作用与剂量相关,其机制可能与降低肺组织TNF-αmRNA表达和抑制NF-κb通路有关。

Protective Effects of Ketamine Pretreatment on Glutamate-Induced Lung Injury in Rats

To evaluate the effects of ketamine pretreatment on glutamate-induced lung injury in rats and the related mechanism. Methods： 50 female SD rats were randomly divided into five groups. Group S was the sham and Group C was the control. 0.75mg/kg Glutamate was used to induce lung injury in group C. In group K5,K10, KS0, ketamine was injected into the abdominal cavity at doses of 5mg/kg, 10mg/kg and 50mg/kg, 20 rain before the intravenous injection of 0.75mg/kg Gluta- mate. Wet/dry ratios of lung tissues,TNF-α mRNA （by RT-PCR） and NF-κb/p65 （by western blot） were detected in each group. The pathology scores in each group were compared. Results： 10 mg/kg and 50mg/kg ketamine pretreatment could de- crease W/D ratio and pathology scores. 10 mg/kg and 50mg/kg ketamine inhibited the up-regulation of TNF-a mRNA in lung tissues, but 5mg/kg ketamine pretreatment did not. Ketamine inhibited the up-regulation of NF-κb/p65. Conclusions： Ket- amine has dose-dependent protective effects on glutamine-induced lung injury in rats, which may be associated with the inhibi- tion of TNF-a mRNA expression and NF-κb/P65 pathway.