中华危重病急救医学
中華危重病急救醫學
중화위중병급구의학
Chinese Critical Care Medicine
2014年
7期
498-502
,共5页
α-黑素细胞刺激素%新型类似物STY39%组织因子途径抑制物%内毒素血症
α-黑素細胞刺激素%新型類似物STY39%組織因子途徑抑製物%內毒素血癥
α-흑소세포자격소%신형유사물STY39%조직인자도경억제물%내독소혈증
α-melanocyte stimulating hormone%Novel analogue STY39%Tissue factor pathway inhibitor%Endotoxemia
目的 研究α-黑素细胞刺激素(α-MSH)及其新型类似物STY39对内毒素血症小鼠产生组织因子途径抑制物(TFPI)的调节作用.方法 按随机数字表法将雌性BALB/c小鼠分为8组,每组9只.经腹腔注射脂多糖(LPS)25 μg/kg和D-氨基半乳糖(D-Gal)100 mg/kg建立内毒素血症小鼠模型;对照组给予磷酸盐缓冲液;实验组于LPS刺激后1、2或3h分别腹腔注射2.5 mg/kg α-MSH或STY39.在LPS刺激后各时间点取眼眶血,并于8h后处死取肺、肝、肾等组织.用酶联免疫吸附试验(ELISA)检测血浆TFPI含量,用逆转录-聚合酶链反应(RT-PCR)检测各组织中TFPI mRNA表达.结果 内毒素血症小鼠血浆TFPI含量(μg/L)于LPS刺激后4h开始升高(11.84± 1.55),8h达高峰(23.49±1.12);LPS刺激后1、2或3h给予α-MSH或STY39均可显著上调血浆TFPI含量,尤其在LPS刺激后1h给药效果最好(LPS刺激后8h取血,α-MSH组:58.79±2.67比28.49±1.69,STY39组:71.08±2.13比28.49±1.69,均P＜0.01),且STY39的作用优于α-MSH(P＜0.01).正常小鼠各组织有少量TFPI mRNA表达;给予LPS刺激后各组织中TFPI mRNA表达升高,尤其在肺、肝和肾组织.LPS刺激后1h给予α-MSH或STY39能显著上调肺、肝组织TFPI mRNA表达(A值,α-MSH肺:51.10±2.89比32.43±2.51,STY39肺:72.11±3.48比32.43±2.51;α-MSH肝:43.21±2.12比29.29±2.06,STY39肝:66.82±1.76比29.29±2.06,均P＜0.01);LPS刺激后1h给予STY39能显著上调肾组织TFPI mRNA表达(A值:45.21±1.80比30.44±2.23,P＜0.01),而给予α-MSH则无明显作用(A值:24.61±1.98比30.44±2.23,P＞ 0.05);早期给予STY39对内毒素血症小鼠肺、肝、肾组织中TFPI mRNA表达的增强作用均优于α-MSH(均P＜0.01).结论 早期给予α-MSH或STY39能促进内毒素血症小鼠产生TFPI,且STY39优于α-MSH.
目的 研究α-黑素細胞刺激素(α-MSH)及其新型類似物STY39對內毒素血癥小鼠產生組織因子途徑抑製物(TFPI)的調節作用.方法 按隨機數字錶法將雌性BALB/c小鼠分為8組,每組9隻.經腹腔註射脂多糖(LPS)25 μg/kg和D-氨基半乳糖(D-Gal)100 mg/kg建立內毒素血癥小鼠模型;對照組給予燐痠鹽緩遲液;實驗組于LPS刺激後1、2或3h分彆腹腔註射2.5 mg/kg α-MSH或STY39.在LPS刺激後各時間點取眼眶血,併于8h後處死取肺、肝、腎等組織.用酶聯免疫吸附試驗(ELISA)檢測血漿TFPI含量,用逆轉錄-聚閤酶鏈反應(RT-PCR)檢測各組織中TFPI mRNA錶達.結果 內毒素血癥小鼠血漿TFPI含量(μg/L)于LPS刺激後4h開始升高(11.84± 1.55),8h達高峰(23.49±1.12);LPS刺激後1、2或3h給予α-MSH或STY39均可顯著上調血漿TFPI含量,尤其在LPS刺激後1h給藥效果最好(LPS刺激後8h取血,α-MSH組:58.79±2.67比28.49±1.69,STY39組:71.08±2.13比28.49±1.69,均P＜0.01),且STY39的作用優于α-MSH(P＜0.01).正常小鼠各組織有少量TFPI mRNA錶達;給予LPS刺激後各組織中TFPI mRNA錶達升高,尤其在肺、肝和腎組織.LPS刺激後1h給予α-MSH或STY39能顯著上調肺、肝組織TFPI mRNA錶達(A值,α-MSH肺:51.10±2.89比32.43±2.51,STY39肺:72.11±3.48比32.43±2.51;α-MSH肝:43.21±2.12比29.29±2.06,STY39肝:66.82±1.76比29.29±2.06,均P＜0.01);LPS刺激後1h給予STY39能顯著上調腎組織TFPI mRNA錶達(A值:45.21±1.80比30.44±2.23,P＜0.01),而給予α-MSH則無明顯作用(A值:24.61±1.98比30.44±2.23,P＞ 0.05);早期給予STY39對內毒素血癥小鼠肺、肝、腎組織中TFPI mRNA錶達的增彊作用均優于α-MSH(均P＜0.01).結論 早期給予α-MSH或STY39能促進內毒素血癥小鼠產生TFPI,且STY39優于α-MSH.
목적 연구α-흑소세포자격소(α-MSH)급기신형유사물STY39대내독소혈증소서산생조직인자도경억제물(TFPI)적조절작용.방법 안수궤수자표법장자성BALB/c소서분위8조,매조9지.경복강주사지다당(LPS)25 μg/kg화D-안기반유당(D-Gal)100 mg/kg건립내독소혈증소서모형;대조조급여린산염완충액;실험조우LPS자격후1、2혹3h분별복강주사2.5 mg/kg α-MSH혹STY39.재LPS자격후각시간점취안광혈,병우8h후처사취폐、간、신등조직.용매련면역흡부시험(ELISA)검측혈장TFPI함량,용역전록-취합매련반응(RT-PCR)검측각조직중TFPI mRNA표체.결과 내독소혈증소서혈장TFPI함량(μg/L)우LPS자격후4h개시승고(11.84± 1.55),8h체고봉(23.49±1.12);LPS자격후1、2혹3h급여α-MSH혹STY39균가현저상조혈장TFPI함량,우기재LPS자격후1h급약효과최호(LPS자격후8h취혈,α-MSH조:58.79±2.67비28.49±1.69,STY39조:71.08±2.13비28.49±1.69,균P＜0.01),차STY39적작용우우α-MSH(P＜0.01).정상소서각조직유소량TFPI mRNA표체;급여LPS자격후각조직중TFPI mRNA표체승고,우기재폐、간화신조직.LPS자격후1h급여α-MSH혹STY39능현저상조폐、간조직TFPI mRNA표체(A치,α-MSH폐:51.10±2.89비32.43±2.51,STY39폐:72.11±3.48비32.43±2.51;α-MSH간:43.21±2.12비29.29±2.06,STY39간:66.82±1.76비29.29±2.06,균P＜0.01);LPS자격후1h급여STY39능현저상조신조직TFPI mRNA표체(A치:45.21±1.80비30.44±2.23,P＜0.01),이급여α-MSH칙무명현작용(A치:24.61±1.98비30.44±2.23,P＞ 0.05);조기급여STY39대내독소혈증소서폐、간、신조직중TFPI mRNA표체적증강작용균우우α-MSH(균P＜0.01).결론 조기급여α-MSH혹STY39능촉진내독소혈증소서산생TFPI,차STY39우우α-MSH.
Objective To evaluate the effect of α-melanocyte stimulating hormone (α-MSH) and its novel analogue STY39 on the production of tissue factor pathway inhibitor (TFPI) in mice with endotoxemia.Methods Female BALB/c mice were randomly divided into eight groups with 9 mice in each group.Endotoxemia was reproduced by intraperitoneal injection of lipopolysaccharide (LPS,25 μg/kg) and D-galactosamine (D-Gal,100 mg/kg).The animals of the control group were given phosphate buffered solution (PBS) instead.In the experimental groups,the mice were injected intraperitoneally with 2.5 mg/kg α-MSH or STY39 at 1,2 or 3 hours following LPS injection.The orbital blood was collected at different time points,and tissues of lung,liver,and kidney were collected 8 hours after the administration of LPS.The plasma TFPI levels were determined by enzyme linked immunosorbent assay (ELISA),and the expression of TFPI mRNA in different tissues was determined with reverse transcription-polymerase chain reaction (RT-PCR).Results The plasma TFPI levels (μg/L) began to increase (11.84 ± 1.55) in the endotoxemia mice 4 hours after LPS challenge and reached the peak (23.49 ± 1.12) at 8 hours.α-MSH or STY39 treatment at 1,2 or 3 hours after LPS challenge could significantly increase the TFPI content,with the best drug effect at 1 hour after LPS challenge (the blood was collected 8 hours after LPS challenge,α-MSH group:58.79 ± 2.67 vs.28.49 ± 1.69,STY39 group:71.08 ± 2.13 vs.28.49 ± 1.69,both P＜0.01),and the effect of STY39 was better than that of α-MSH (P＜0.01).A small amount of TFPI mRNA expression was observed in each tissue of the healthy mice.After LPS challenge,TFPI mRNA expression was increased in all the tissues,especially in the lung,liver and kidney.α-MSH or STY39treatment at 1 hour after LPS challenge could significantly up-regulate the expression of TFPI mRNA in the lung and liver (A value,α-MSH in lung:51.10 ±2.89 vs.32.43 ±2.51,STY39 in lung:72.11 ±3.48 vs.32.43 ±2.51;α-MSH in liver:43.21 ± 2.12 vs.29.29 ± 2.06,STY39 in liver:66.82 ± 1.76 vs.29.29 ± 2.06,both P＜0.01).The treatment with STY39 at 1 hour after LPS challenge could significantly up-regulate the expression of TFPI mRNA in the kidney (A value:45.21 ± 1.80 vs.30.44 ± 2.23,P＜0.01),but the treatment with α-MSH had no obvious effect (A value:24.61 ± 1.98 vs.30.44 ± 2.23,P＞0.05).The enhancing effect of early administration of STY39 on TTPI mRNA expression in the lung,liver and kidney tissues of endotoxemia mice was more powerful than that of α-MSH (all P＜0.01).Conclusion The early administration of α-MSH or STY39 may up-regulate TFPI production in the mice with endotoxemia,and the effect of STY39 is superior to α-MSH.
