利拉鲁肽对脓毒症诱导急性呼吸窘迫综合征小鼠的保护作用研究  

Research progress in protective effects of liraglutide on sepsis induced acute respiratory distress syndrome in mice

作　　者：周锋[1] 李志锋[2] 王志力[2] 靳风[2] 张颖[2] ZHOU Feng;LI Zhifeng;WANG Zhili;JIN Feng;ZHANG Ying(Department of ICU,Zhongnan HospitalDepartment of Endocrinology,ChinaHubei 430071;Department of ICU,Zhongnan HospitalWuhan University,Wuhan,ChinaHubei 430071)

机构地区：[1]武汉大学中南医院内分泌科,武汉430071 [2]武汉大学中南医院重症医学科,武汉430071

出　　处：《重庆医学》2019年第4期569-572,共4页Chongqing medicine

摘　　要：目的观察利拉鲁肽对脓毒症诱导产生急性呼吸窘迫综合征(ARDS)小鼠的保护作用。方法将30只雄性BABL/c小鼠分为3组:对照组、ARDS组、利拉鲁肽干预组。对照组及ARDS组小鼠先给予生理盐水皮下注射,利拉鲁肽干预组小鼠给予利拉鲁肽皮下注射。利拉鲁肽干预6h后,ARDS组及利拉鲁肽干预组小鼠给予10mg/kg脂多糖腹腔注射,对照组小鼠腹腔注射等体积生理盐水;脂多糖注射4h后,取左肺上叶组织做病理学检测,左肺下叶检测肺组织湿/干重(W/D)比值,测定肺泡灌洗液(BALF)中蛋白水平、白细胞介素-1β(IL-1β)及白细胞介素-18(IL-18)水平,检测肺组织NLRP3、ASC及caspase-1mRNA表达。结果腹腔注射脂多糖4h后,ARDS组小鼠肺组织病理切片提示肺组织内出现大量炎性细胞浸润及蛋白渗出,利拉鲁肽干预组小鼠肺组织病理学改变明显减轻。ARDS组小鼠肺W/D比值[(6.01±0.32)vs.(3.37±0.25)]、BALF中蛋白水平[(0.79±0.08)g/L vs.(0.22±0.01)g/L]、IL-1β[(582.70±65.21)pg/mL vs.(167.20±25.56)pg/mL]、IL-18[(179.50±22.25)pg/mL vs.(68.50±11.15)pg/mL]均明显高于对照组(P<0.05),而利拉鲁肽干预组小鼠肺组织W/D比值(4.72±0.12)、BALF中蛋白水平[0.51±0.05)g/L]、IL-1β水平[(399.70±38.56)pg/mL]、IL-18水平[(122.80±14.28)pg/mL]均明显低于ARDS组(P<0.05);ARDS组小鼠肺组织NLRP3、ASC及caspase-1mRNA表达量[(4.97±0.35)vs.(1.06±0.11)]、[(3.62±0.21)vs.(1.08±0.09)]、[(2.37±0.25)vs.(0.96±0.07)]均明显高于对照组,而利拉鲁肽干预组小鼠肺组织NLRP3、ASC及caspase-1mRNA表达量[(3.21±0.28)、(1.91±0.18)、(1.63±0.12)]均明显低于ARDS组(P<0.05)。结论利拉鲁肽干预对脓毒症诱导的急性呼吸窘迫综合征小鼠具有保护作用。Objective To investigate the effects of liraglutide on sepsis induced acute respiratory distress syndrome (ARDS) in mice. Methods Thirty Balb/c female mice were randomly divided into the three groups:control group,ARDS group and liraglutide intervention group.The control group and ARDS group were given normal saline by subcutaneous injection,and liraglutide intervention group was given liraglutide by subcutaneous injection.After liraglutide intervention for 6 h,the ARDS group and liraglutide group were given 10 mg/kg LPS by peritoneal injection,while the control group was peritoneal injected by the same volume of normal saline.After 4 h of LPS injection,the left upper and lower lung tissues were taken for conducting the pathological examination and detecting the wet/dry (W/D) ratio respectively.The protein levels,interleukin-1β(IL-1β) and interleukin-18(IL-18) levels in bronchoalveolar lavage fluid (BALF) were detected.Moreover,the expressions of nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3),apoptosis-associated speck-like protein (ASC) and caspase-1 were detected. Results The lung tissue pathological section at 4 h after LPS peritoneal injection indicated that a large number of inflammatory cells infiltration and protein exudation in the ARDS group,and the pathology changes were significantly alleviated in the liraglutide group. The level of W/D ratio [(6.01±0.32) vs .(3.37±0.25)],protein level in BALF [(0.79±0.08)g/L vs .( 0.22± 0.01) g/L],IL-1β[(582.70±65.21)pg/mL vs .( 167.20±25.56) pg/mL],IL-18 [(179.50±22.25)pg/mL vs .( 68.50±11.15)pg/mL] in the ARDS group were significantly higher than those in the control group ( P < 0.05),while the level of W/D ratio(4.72±0.12),protein level in BALF (0.51±0.05 )g/L,IL-1β level (399.70±38.56) pg/mL and IL-18 level (122.80±14.28) pg/mL in the liraglutide intervention group were significantly lower than those in the ARDS group( P <0.05).The expression levels of NLRP3,ASC and caspase-1 mRNA in lung tissue [(4.97±0.35) vs .(1.06±0

关 键 词：呼吸窘迫综合征 成人 脓毒症 利拉鲁肽 炎性反应 

分 类 号：R826.3[医药卫生—临床医学]