远志皂苷元对脓毒症大鼠预后和急性肺损伤的影响

Effects of senegenin on prognosis and acute lung injury in septic rats

目的探讨远志皂苷元(SEN)对脓毒症大鼠预后和急性肺损伤(ALI)的影响。方法将150只健康雄性SD大鼠随机分为5组,分别为脓毒症模型组〔盲肠结扎穿孔术(CLP)组:采用CLP建立脓毒症大鼠模型〕、脓毒症+SEN组(CLP/S组)、脓毒症+二甲基亚砜(DMSO)组(CLP/D组)、假手术组(Sham组)及空白对照组,每组30只。CLP/S组大鼠分别于制模前4 h及制模后4 h腹腔注射SEN 15 mg/kg,此后每日注射1次,持续至术后4 d,其余处理同CLP组;CLP/D组大鼠腹腔注射等体积二甲基亚砜溶液,其余处理同CLP组;Sham组大鼠仅开腹取出盲肠探查后还纳腹腔,不进行结扎和穿孔;空白对照组大鼠不予处理。观察建模后7 d内各组大鼠的存活情况。另取100只健康雄性SD大鼠,随机分为5组,分组方法和实验处理同前,24 h后麻醉处死大鼠,取左肺组织测量肺湿/干质量(W/D)比值及肺水含量,取右下肺组织进行病理切片,苏木素-伊红(HE)染色并计算病理形态学积分。结果与空白对照组和Sham组相比,CLP组、CLP/S组、CLP/D组大鼠术后7 d内的死亡率增加,尤以CLP组、CLP/D组增加显著〔53.33%(16/30)、53.33%(16/30)比0%(0/30)、3.33%(1/30),均P<0.05〕;与CLP组、CLP/D组大鼠相比,CLP/S组大鼠的死亡率明显降低〔20.00%(6/30)比53.33%(16/30)、53.33%(16/30),均P<0.05〕;术后7 d内CLP、CLP/D两组大鼠的存活情况无显著差异。与空白对照组和Sham组比较,CLP组、CLP/D组、CLP/S组的W/D比值、肺水含量和病理形态学积分均升高〔W/D比值:4.60±0.39、4.56±0.19、4.29±0.36比4.06±0.43、4.14±0.23,肺水含量:(78.21±1.81)%、(77.93±1.03)%、(76.67±1.91)%比(75.00±2.67)%、(75.80±1.32)%,病理形态学积分:11.50±1.38、9.67±3.33、5.00±1.67比0、0.33±0.52〕,除CLP/S组大鼠W/D比值及肺水含量增加差异均无统计学意义(均P>0.05)外,其余指标差异均有统计学意义(均P<0.05)。但CLP/S组大鼠的W/D比值、肺水含量及病理形态学积分均明显低于CLP组和CLP/D组。结论SEN可减轻脓毒症所致ALI的症状,降低脓毒症大鼠死亡率。

Objective To observe the effects of senegenin(SEN)on outcome and acute lung injury(ALI)in septic rats.Methods Totally 150 healthy male SD rats were randomly divided into 5 groups:sepsis model group[cecal ligation and perforation(CLP)group:the sepsis rat model was established by CLP],sepsis-SEN group(CLP/S group),sepsis-dimethyl sulfoxide group(CLP/D group),sham control group(Sham group)and blank control group,with 30 rats in each group.Rats in CLP/S group were injected intraperitoneally with 15 mg/kg of SEN 4 hours before and 4 hours after CLP,and then injection once per day with the same method and dose of SEN for consecutive 4 days after CLP,the other management was the same as that in CLP group;while in the rats in CLP/D group,equivalent volume of dimethyl sulfoxide(DMSO)solution was intraperitoneally given and the other treatment was the same as that in CLP group;in Sham group,the rats received laparotomy,cecum taken out for examination and then returned back to its original place without cecal ligation and puncture;the rats in blank control group did not accept any treatment.The survival situations in each group within 7 days after surgery were recorded.The mortalities of rats in each group on 1,2,3 and 7 days after operation were calculated.Other 100 health male SD rats were randomly divided into five groups and received the same group classification method and experimental treatments as above.After 24 hours,the rats were anesthetized and sacrificed by exsanguinations,and the left lung tissues were collected to measure the wet/dry weight(W/D)ratio of lungs and lung water content.The right lower lung tissues were taken to carry out hematoxylin-eosin(HE)staining and histological section examination and calculate the score of morphologic lung changes.Results Compared with blank control and Sham groups,the mortality in postoperative 7 days in CLP,CLP/S and CLP/D groups increased,particularly the CLP and CLP/D groups increased significantly[53.33%(16/30),53.33%(16/30)vs.0%(0/30),3.33%(1/30),all P<0.05];compared with CLP and CLP/D groups,the mortality in CLP/S group decreased significantly[20.00%(6/30)vs.53.33%(16/30),53.33%(16/30),both P<0.05];there was no obvious difference in survival situation between CLP and CLP/D groups.Compared with blank control and Sham groups,the W/D ratio,lung water content and morphological change scores in CLP,CLP/D and CLP/S groups were higher[W/D ratio:4.60±0.39,4.56±0.19,4.29±0.36 vs.4.06±0.43,4.14±0.23,lung water content:(78.21±1.81)%,(77.93±1.03)%,(76.67±1.91)%vs.(75.00±2.67)%,(75.80±1.32)%,pathological morphological change score:11.50±1.38,9.67±3.33,5.00±1.67 vs.0.33±0.52].Except that there was no significant difference in the increase of W/D and lung water content in CLP/S group(all P>0.05),there were significant differences in other indexes(all P<0.05).However,the W/D ratio,lung water content and pathomorphological score of CLP/S group were significantly lower than those of CLP group and CLP/D group.Conclusion SEN can alleviate sepsis-induced ALI and reduce the mortality rate of septic rats.