吸入不同浓度异氟醚对大鼠肺脏磷脂合成的影响

Effects of isoflurane on synthesis of phosphatidylcholine in adult rat lungs

目的探讨吸入不同浓度异氟醚(Iso)对正常大鼠肺脏磷脂酰胆碱(PC)合成代谢的影响。方法78只Wistar大鼠随机取出6只设为空白组(E组),吸入空气。剩余大鼠随机均分为四组,每组又分为吸入4、8h和吸入8h停药2h亚组,每亚组6只。采用高效液相色谱法(HPLC法)测定支气管肺泡灌洗液(BALF)中PC浓度,RT-PCR和蛋白质免疫印迹法(WesternBlot)分别检测肺组织磷酸胆碱二胞苷酰基转移酶(CCT)基因及其蛋白的表达。结果各组间肺组织CCTmRNA和匀浆中CCT蛋白的表达差异无统计学意义。B2组、C2组BALF中PC含量及肺组织微粒体CCT蛋白的表达量均低于E组和B1组、C1组(P<0.05),停药后2h恢复。吸入Iso8h时,B2组、C2组BALF中PC含量及肺组织微粒体CCT蛋白的表达量均低于D2组(P<0.05),同时C2组低于A2组(P<0.05)。结论长时间吸入较高浓度的异氟醚可降低大鼠正常肺脏磷脂合成水平,其机制可能与CCT活性降低有关。

Objective To investigate whether inhaled different concentrations of isoflurane （Iso） may affect the synthesis of phosphatidylcholine （PC） in mature lungs. Methods Seventy-eight adult male Wistar rats were randomly divided into four groups. Furthermore, for each of group A to D, 3 subgroups （n=6） were established according to the duration of the gas administration. High performance liquid chromatography （HPLC） was employed to deter mine the PC concentration in bronchoalveolar lavage fluid （BALF）. The mRNA expression and protein of cytidine triphosphate.. phosphochollne cytidylyltransferase （CCT） were measured by reverse transcription polymerase chain reaction（RT-PCR） and Western blot. Results The level of mRNA and protein of CCT in lung homogenates were not significantly different among all groups. Compared with group E and 4 h subgroup, in group B2 and C2, both the PC concentration in BALF and the expression of microsomal CCT in pulmonary tissue reached the nadir （P〈0.05） and recovered at 2 hours after the cessation. During 8 h exposure, in group P,2 and C2, the PC concentration and the expression of mlcrosomal CCT were lower than in group D2 （P〈0.05）, while both parameters in group C2 were also lower than in group A2 （P 〈 0.05）. Conclusion Isoflurane （ 1.5 %, 2.0 %） inhalation for a longer duration （8 hours） may reversibly impair the de novo phospholipids synthesis in rat lung, of which the mechanism may be associated with the decreased activity of CCT.