生长抑素对百草枯中毒小鼠急性肾损伤的保护作用和机制研究  

Study on the protective effect and mechanism of somatostatin on renal injury in paraquat intoxicated mice

作　　者：杨浙宁 曹凯强 许昌琴 何忆月 洪广亮[2] 卢中秋[2] Yang Zhening;Cao Kaiqiang;Xu Changqin;He Yiyue;Hong Guangliang;Lu Zhongqiu(Emergency Department of the Yiwu Hospital Affiliated to Wenzhou Medical University,Yiwu 322000,China;Emergency Department of the First Affiliated Hospital of Wenzhou Medical University,Yiwu 325000,China;Sun Yat-sen Memorial Emergency Department of Hospital Sun Yat-sen University,Guangzhou 510120,China)

机构地区：[1]温州医科大学附属义乌医院,义乌322000 [2]温州医科大学附属第一医院急诊科,义乌325000 [3]中山大学孙逸仙纪念医院南院区急诊科,广州510120

出　　处：《中华劳动卫生职业病杂志》2020年第6期410-415,共6页Chinese Journal of Industrial Hygiene and Occupational Diseases

摘　　要：目的探讨生长抑素(SS)对百草枯(PQ)中毒小鼠急性肾损伤(AKI)的保护作用及其机制。方法 2017年12月至2018年4月,选择SPF级雄性BALB/C小鼠48只,随机分为4组每组12只,PQ组和PQ+SS组小鼠用60 mg/kg PQ灌胃,对照组和SS组以等剂量生理盐水灌胃,PQ+SS组和SS组小鼠在灌胃前1 h及灌胃后3 h各向腹腔注射1次SS(20 ml/kg)。对照组和PQ组在相同时间腹腔注射等剂量生理盐水。观察小鼠一般情况和行为学的影响。在造模24 h后处死小鼠,摘除眼球后取血,剖腹取出双肾,ELISA法分别测定血清白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)和髓过氧化物酶(MPO)水平;光镜下观察中毒性肾小管损伤特征性病理改变并以此为评分;免疫印迹法(Western blot)检测核因子-κB(NF-κB)表达变化情况,化学比色法检测肾组织超氧化物歧化酶(SOD)、半胱氨酸天冬氨酸蛋白酶-3(Caspase-3)、丙二醛(MDA)等指标的变化。结果对照组和SS组小鼠一般情况和行为基本正常;与对照组比较,PQ组小鼠表现为进食、活动减少,皮毛干燥、倒毛,精神萎靡;与PQ组比较,PQ+SS组小鼠症状均减轻。光镜下PQ组小鼠肾组织结构明显紊乱,被严重破坏,肾病理学评分(6.14±0.72)分;与PQ组比较,PQ+SS组小鼠肾病理学评分[(4.36±0.42)分]下降(P<0.05)。与对照组比较,PQ组小鼠血清TNF-α(39.89±3.32)pg/ml、IL-6(77.29±4.77)pg/ml、NF-κB(2.29±0.10)、MPO(0.31±0.02)μg/ml、MDA(0.91±0.03)mmol/mg prot、Caspase-3(376.51±8.24)%水平测定明显升高,肾组织SOD表达明显下降[(2.36±0.73)U/mg prot](P<0.05)。与PQ组比较,PQ+SS组小鼠血清TNF-α(33.82±1.57)pg/ml、IL-6(58.49±5.89)pg/ml、肾组织NF-κB(0.84±0.05)、MPO(0.22±0.01)μg/ml、肾组织MDA(0.72±0.05)mmol/mg prot、Caspase-3(327.32±21.93)%水平下降明显,肾组织SOD表达明显上升[(4.90±0.81)U/mg prot](P<0.05)。结论 PQ中毒可导致小鼠AKI,而SS能减轻PQ中毒引起的AKI,改善PQ中毒小鼠的一般生存状态,对PQ�Objective To investigate the protective effect of somatostatin(SS)on acute kidney injury(AKI)of paraquat(PQ)poisoned mice and its mechanism.Methods From December 2017 to April 2018,a total of 48 SPF male BALB/C mice were selected and randomly divided into 4 groups,with 12 mice in each group:Control group,SS group(20 mg/kg SS was injected 1 hour before and 3 hours after gavage with normal saline),PQ group(2%PQ 60 mg/kg by gavage)and PQ+SS group(Intragastric administration was performed with 2%PQ solution of 60 mg/kg,and 20 mg/kg SS was administered 1 h before and 3 h after intragastric administration),12 mice in each group were observed for the general situation and behavioral effects.After 24 hours of modeling,mice were sacrificed.Then blood was extracted after eyeball was removed,and both kidneys were removed by laparotomy.Serum IL-6,TNF-αand MPO levels were determined by ELISA.The characteristic pathological changes of toxic renal tubular injury were observed under light microscope and scored accordingly.The changes of NF-κB expression were detected by Western-Blot,SOD,Caspase-3 and malondialdehyde(MDA)were detected by chemical colorimetry.Results Mice in Control group and SS group showed normal general conditions and behaviors;Mice in PQ group were significantly worse than those in Control group,showing decreased feeding and activity,dry fur,hair shedding and listless spirit;The above symptoms in the mice of PQ+SS group were alleviated compared with the PQ group.Under the light microscope,the renal tissue structure of PQ group was obviously disordered and severely damaged,and the nephropathy score was(6.14±0.72).The performance of PQ+SS group under light microscope was improved compared with PQ group,and nephropathy score(4.36±0.42)decreased(P<0.05).Compared with the Control group,serum TNF-α(39.89±3.32)pg/ml,IL-6(77.29±4.77)pg/ml,renal NF-κB(2.29±0.097),MPO(0.31±0.017)μg/ml,MDA(0.91±0.03)mmol/mg prot,and Caspase-3(376.51±8.24)%levels were significantly increased in the PQ group,while the level of

关 键 词：生长抑素 中毒 急性肾损伤 氧化应激 炎症反应 肾小管损伤病理学评分 

分 类 号：R965[医药卫生—药理学]