血必净注射液对脓毒症大鼠营养代谢的影响

目的:观察血必净注射液对脓毒症大鼠血糖、血脂、血浆蛋白等营养物质含量的影响.方法:健康雄性wistar大鼠60只随机分为对照组(n=20)、脓毒症组(n=20)和血必净治疗组(n=20).脓毒症组、血必净治疗组于注射内毒素(LPS)后0.5 h分别尾静脉注射4 mL/kg生理盐水(NS)和血必净注射液,正常对照组予以注射4mL/kg NS.在注射NS/LPS后2、6、12、24 h,经颈动脉取血用于检测血浆血糖、血脂、血浆总蛋白和白蛋白值.结果:脓毒症组大鼠在LPS尾静脉注射后2 h,血糖浓度开始升高,6 h后达到高峰,并且血糖浓度一直处于较高水平,而血必净和对照组比较,血糖变化无统计学意义.血必净组2 h后甘油三酯、极低密度脂蛋白升高明显,12、24 h后各血脂指标和对照组比较无统计学意义.脓毒症组大鼠24 h后总蛋白、白蛋白明显下降,而血必净和对照组比较不明显.结论:脓毒症早期应用血必净注射液可以控制血糖,减少脂蛋白的参与炎症复合物的形成,减少血浆蛋白分解.     

血必净对脓毒症大鼠肠黏膜屏障及巨噬细胞抗体表达的作用

目的 观察血必净对脓毒症大鼠肠黏膜屏障和巨噬细胞抗体表达的变化的影响作用,探讨其在脓毒症发病中的作用机制及意义.方法 Wistar大鼠150只,分成脓毒症组、血必净干预组和假手术组.采用肓肠结扎穿孔术建立脓毒症大鼠模型,模型标准是发热、呼吸频率增加、心率加快和白细胞总数改变.血必净组大鼠术前12 h、术后腹腔内注射4 mL/kg血必净,1次/12 h,共3 d;其余两组大鼠同时注射相同体积的生理盐水.利用图像分析系统检测三组大鼠肠黏膜病理变化和巨噬细胞的表达水平,并运用等级资料秩和检验和方差分析进行统计学分析.结果 假手术组大鼠小肠黏膜多为基本正常黏膜,12 h,24 h,48 h,72 h脓毒症组、血必净组大鼠肠道黏膜出现病变;脓毒症组病变较血必净组更为严重,差异具有统计学意义(H=19.732,P<0.01).在0 h三组小肠黏膜巨噬细胞抗体的表达数基本一致,12 h,24 h,48 h,72 h脓毒症组和血必净组间差异具有统计学意义,且均较C组变化差异具有统计学意义(F=560.13,P<0.05).结论 脓毒症大鼠肠道黏膜机械屏障和免疫屏障均有不同程度的损害,血必净注射液可部分保护肠道黏膜机械屏障和免疫屏障.     

血必净注射液对创伤弧菌脓毒症大鼠肺组织Toll样受体4及核转录因子-κB表达的影响

目的 观察血必净注射液对创伤弧菌脓毒症大鼠肺组织Toll样受体4(TLR4)mRNA表达和核转录因子-κB(NF-κB)活性的干预作用.方法 将110只SD大鼠随机分为正常对照组、模型组、血必净干预组,后两组再分为染菌后1、6、12、24、48 h亚组,每组10只大鼠.于大鼠左后肢皮下注射创伤弧菌悬液制备创伤弧菌脓毒症模型;血必净组于染菌后0.5 h腹腔注射血必净注射液4 ml/kg.各时间点处死大鼠取肺组织,检测肺组织湿/干重比值(W/D比值)、TLR4 mRNA表达、NF-κB活性和肿瘤坏死因子-α(TNF-α)含量.结果 模型组大鼠肺组织W/D比值于染菌后6、12、24、48 h明显高于正常对照组,而血必净组24 h、48 h较模型组明显减小(均P<0.05).模型组大鼠肺组织TLR4 mRNA表达在染菌后6、12、24 h明显高于正常对照组,而血必净组6 h较模型组明显减少(均P<0.05).模型组大鼠肺组织NF-κB活性在染菌后1、6、12 h明显高于正常对照组,而血必净组1 h、6 h较模型组明显降低,24 h、48 h较模型组明显升高(均P<0.05).模型组大鼠肺组织TNF-α于染菌后1、6、12、24 h明显高于正常对照组,而血必净组12 h较模型组明显降低(均P<0.05).结论 TLR4-NF-κB通路参与了创伤弧菌脓毒症肺损伤的早期病理生理过程;血必净注射液能抑制TLR4-NF-κB活化,减轻创伤弧菌脓毒症大鼠肺损伤.     

血必净注射液对脓毒症大鼠纤溶系统功能的影响

目的 观察血必净注射液对脓毒症早期循环及纤溶系统功能的影响.方法 采用盲肠结扎穿孔术(CLP)制备脓毒症大鼠模型.75只雄性SD大鼠按随机数字表法分为假手术组、模型组和血必净组,各组按处死时间又分为术后2、4、6、8、12 h 5个亚组,每组5只.假手术组和模型组术后即刻静脉补充生理盐水;血必净组术后1 h内给予血必净注射液,之后补充生理盐水.每小时监测平均动脉压(MAP);各组于相应时间点取血检测血浆组织型纤溶酶原激活物(t-PA)及其抑制物(PAI)含量.结果 假手术组MAP有所下降,但在正常范围内;模型组和血必净组MAP均下降,并逐渐进入休克状态,11 h和12 h MAP与假手术组相比差异有统计学意义(P<0.05或P<0.01).假手术组血浆t-PA含量无明显变化;模型组血浆t-PA含量在术后2 h即明显高于假手术组,之后逐渐下降,至12 h仍高于假手术组(P<0.05或P<0.01);血必净组血浆t-PA含量在术后2 h即高于假手术组,之后逐渐升高,且于术后6、8、12 h显著高于模型组(P<0.05或P<0.01).假手术组血浆PAI含量无明显变化;模型组血浆PAI含量在术后4 h明显高于假手术组(P<0.05),之后降至假手术组水平,12 h时明显低于假手术组(P<0.05);血必净组在术后6、8、12 h PAI显著高于假手术组和模型组(均P<0.01).结论 血必净注射液对脓毒症大鼠早期循环功能有一定的改善作用,并能促进纤溶系统的激活,从而改善脓毒症早期机体的高凝状态.     

血必净对创伤弧菌脓毒症大鼠肺组织核因子-κB p65表达作用的研究

目的 观察创伤弧菌脓毒症大鼠肺组织核因子-κB(NF-κB)p65基因及蛋白表达,并探讨血必净对其的干预作用.方法 SD大鼠110只,随机分为正常组(A组,n＝10)、创伤弧菌脓毒症组(B组,n＝50,采用大鼠左下肢皮下注射创伤弧菌悬液制作大鼠创伤弧菌脓毒症模型)和血必净治疗干预组(C组,n＝50,感染后半小时腹腔注射血必净4 mL/kg).B、C组于染菌后1、6、12、24、48 h活杀(各时间点n=10),采用逆转录-聚合酶链式反应(RT-PCR) 法、Western blot法和双抗体夹心酶联免疫吸附法(ELISA)分别检测大鼠肺组织NF-κB p65的基因与蛋白表达及IL-10的含量,数据采用单因素方差分析.结果 与A组比较,B组大鼠肺组织创伤弧菌感染后6、12 h NF-κB p65 mRNA表达量与6、12、24和48 h肺组织NF-κB p65蛋白表达量均明显增高 (P<0.05);与B组相同时间点比较,C组6 h肺组织NF-κB p65 mRNA表达量与12、24及48 h肺组织NF-κB p65 蛋白表达量明显减少(P<0.05); 与A组比较,B组创伤弧菌菌感染12、24和48 h IL-10的含量明显增加(P<0.05),与B组相同时间点比较,C组24 h(52.444±9.605)肺组织IL-10的含量明显增高(P<0.05);感染后48 h,大鼠肺内血管明显充血,间质水肿并伴炎性浸润,肺泡腔塌陷,血必净干预后,肺组织损伤有所减轻.结论 NF-κB参与了创伤弧菌脓毒症肺损伤过程;血必净能抑制NF-κB p65的表达,从而起到保护创伤弧菌脓毒症大鼠肺组织的作用.     

辛伐他汀预处理对脓毒症大鼠凝血功能及肝脏C-反应蛋白的影响

目的 观察辛伐他汀预处理对脓毒症大鼠凝血功能及肝脏C-反应蛋白(CRP)的影响.方法 采用盲肠结扎穿孔术(CLP)制备脓毒症大鼠模型.清洁级雌性Wistar大鼠80只被随机分为正常对照组(8只)、假手术组(6、24、48 h各8只)、脓毒症模型组(6、24、48 h各8只)和辛伐他汀预处理组(6、24、48 h各8只),除正常对照组外,其余各组于CLP术前给予生理盐水或辛伐他汀20 mg/(kg·d)(溶于1 mL蒸馏水),灌胃连续2周,各组分别于CLP术后6、24、48 h后活杀动物8只,留取血液及肝组织标本.观察脓毒症大鼠一般表现并测定脓毒症大鼠白细胞计数(WBC)及血小板计数(PLT)、组织因子(TF)、纤溶酶原激活物抑制物-1(PAI-1)、肝脏CRP等指标.结果 辛伐他汀预处理可以降低脓毒症大鼠TF、PAI-1水平,减少PLT消耗,同时降低肝脏组织CRP水平的表达.结论 辛伐他汀预处理能够改善脓毒症大鼠的凝血功能;减轻肝脏炎症反应,保护肝脏功能.     

血必净注射液对烧伤延迟复苏大鼠器官功能及死亡率的影响

目的 观察血必净注射液对烧伤延迟复苏大鼠多器官功能损害和死亡率的影响。方法 采用大鼠30％总体表面积Ⅲ度烫伤模型。130只雄性Wistar大鼠按随机数字表法分为假伤组（n=10）、烫伤组（n=60，伤后6h腹腔内注射40ml／kg生理盐水）和血必净组（n=60，血必净注射液4ml／kg，每日2次）。除假伤组外，各组再根据不同给药时间点分为伤前2h（n=20）、伤后2h（n=20）和伤后12h（n=20）给药组。分别观察不同时间点各组动物7d的死亡率及伤后12h多器官功能改变。结果 与烫伤组相比，伤后12h血必净组动物死亡率显著降低（75．0％比40．0％。P〈0．05）；同时，血必净组伤后12h血清丙氨酸转氨酶（ALT）、天冬氨酸转氨酶（AST）、尿素氮（BUN）、肌酐（Cr）及肌酸激酶（CK）水平均明显降低（P〈0．05或P〈0．01）。结论 血必净注射液能够明显降低严重烧伤延迟复苏大鼠的死亡率，并对重要器官具有保护作用。     

血必净注射液对脓毒性休克大鼠器官微观结构的影响

目的：观察血必净注射液对脓毒性休克大鼠器官微观结构的影响。方法选择清洁级雄性SD大鼠15只,按随机数字表法分为假手术组、模型组和血必净组,每组5只。采用盲肠结扎穿孔术（CLP）制备腹腔感染致脓毒性休克大鼠模型;假手术组仅行腹腔正中切开,探查腹腔,翻动盲肠后关腹。血必净组术后1h内经股静脉插管给予血必净注射液4 mL/kg,之后以生理盐水2 mL·kg-1·h-1持续输注至处死之前;假手术组和模型组术后给予等量生理盐水。所有大鼠经右侧颈动脉置管接压力装置连续监测血压变化,观察至12 h后处死大鼠留取心、肺、肝及肾脏标本,电镜下观察超微结构的改变。结果假手术组血压随时间延长轻微下降,但基本正常。模型组于术后9 h、血必净组约在术后10 h进入休克状态,平均动脉压（MAP）低于70 mmHg （1 mmHg＝0.133 kPa）;术后11 h,模型组和血必净组MAP均较假手术组明显降低（mmHg：58.7±7.0、58.7±8.3比91.0±8.2,均P＜0.01）,术后12 h持续降低,但血必净组略高于同期模型组（mmHg：55.4±4.0比48.8±12.9, P＞0.05）。电镜下观察可见：假手术组心、肺、肝及肾各器官结构基本正常;模型组各器官均出现不同程度的结构损伤;而血必净组大鼠心脏和肺脏的损伤较模型组减轻,特别是细胞内线粒体改变明显,肾脏及肝脏的损伤较模型组无明显变化。结论血必净注射液对稳定脓毒性休克大鼠循环系统有一定的作用,并有可能减轻感染及休克对大鼠心脏和肺脏的损伤。     

血必净注射液对急性肺损伤大鼠氧自由基变化的影响

目的:探讨血必净注射液对急性肺损伤大鼠氧自由基变化的影响.方法:SD大鼠72只随机分为正常对照组、内毒素组(LPS组)和内毒素联合血必净组(LPS+XBJ组),后两组又分别分为给药后1、2、4、12 h 4个亚组,每个亚组8只.采用静脉注射LPS(5 mg/kg)建立急性肺损伤模型.LPS+XBJ组予静脉注射LPS后同时腹腔注射血必净(10 mL/kg),LPS组腹腔注射等量生理盐水(10 mL/kg),正常对照组给予等量生理盐水.观察各组肺组织病理学变化,检测各组肺湿干质量比(W/D)、血清丙二醛(MDA)浓度、超氧化物歧化酶(SOD)活力等的变化.结果:血必净注射液干预可显著降低急性肺损伤大鼠升高的W/D(P<0.05)和血清肺MDA浓度(P<0.01或P<0.05).显著升高急性肺损伤大鼠降低的SOD浓度(P<0.01或P<0.05),减轻肺组织形态学损伤.结论:血必净注射液可抑制氧自由基产生.对LPS所致急性肺损伤大鼠具有肺保护作用.     

血必净注射液与活化蛋白C对脂多糖诱导大鼠单核细胞组织因子干预效果的比较研究

目的 比较血必净注射液与活化蛋白C(APC)对脂多糖(LPS)刺激大鼠单核细胞表达组织因子(TF)及蛋白酶激活受体1(PAR-1)的影响.方法采用黏附法分离正常大鼠外周血单核细胞后,按随机数字表法分为正常对照组、LPS刺激组、LPS+APC组和LPS+血必净组.分别于LPS刺激后12、24、48、72 h收集细胞,用流式细胞仪检测PAR-1表达的荧光强度;同时留取细胞培养上清液,采用酶联免疫吸附法(ELISA)检测TF、白细胞介素-6(IL-6)和肿瘤坏死因子-α(TNF-α)水平.结果 LPS刺激组24 h后各时间点大鼠单核细胞PAR-1的荧光强度较正常对照组显著升高,各时间点上清液中TF、IL-6、TNF-α水平也明显高于正常对照组(P均<0.01).与LPS刺激组比较,LPS+APC组和LPS+血必净组PAR-1、TF、IL-6、TNF-α水平均显著降低(P<0.05或P<0.01);且LPS+血必净组24 h、48 h时PAR-1、TF、TNF-α水平均显著低于LPS+APC组(P<0.05或P<0.01).结论血必净注射液和APC均可显著降低LPS刺激大鼠单核细胞PAR-1表达,减少TF、IL-6、TNF-α分泌,血必净的作用较APC明显.     

脓毒症大鼠肠黏膜免疫屏障功能的变化

目的 研究脓毒症对大鼠肠黏膜免疫屏障功能的影响.方法 60只SD大鼠随机(随机数字法)分为对照组(n=15)和脓毒症组(n=45),采用盲肠结扎穿孔术(CLP)建立脓毒症模型.模型建立后3 h、6 h和12 h留取回肠黏膜和全血标本.分别进行肠黏膜形态学观察、肠防御素5(RD-5)及肠三叶因子3(TFF_3)Mrna表达水平检测、肠黏膜淋巴细胞凋亡分析,以及外周血中肠源性细菌DNA定性检测.结果 CLP所致脓毒症导致大鼠回肠黏膜明显损害,主要表现为上皮脱落、固有层分离、毛细血管出血和溃疡形成;脓毒症组模型建立后3 h即出现RD-5和TFF_3 Mrna表达显著性减少(与正常组比较,P<0.05),且6 h和12 h组进行下降(与3 h组比较,P<0.05),肠黏膜淋巴细胞凋亡数亦显著增加(P<0.05);同时,脓毒症组全血肠源性细菌DNA扩增全部阳性.结论 脓毒症时大鼠肠黏膜免疫屏障功能显著减退,且随脓毒症的发展而进行性恶化.     

血必净调节脓毒症脾组织Fas Bax蛋白表达改善免疫麻痹的实验研究

目的观察血必净对脓毒症大鼠脾组织促调亡相关蛋白表达及细胞免疫功能的影响。方法96只Wistar大鼠随机分为正常对照组(8只)、假手术组(8只)、模型组(40只)和血必净组(40只),以盲肠结扎穿孔法(CLP)制备脓毒症模型。ELISA法检测血清IL-2、IL-10水平,免疫组化法检测脾组织Fas、Bax蛋白表达水平。结果模型组大鼠脾组织Fas、Bax表达明显增多,同时于造模后36、48h,血清IL-2水平明显下降,IL-10水平显著升高。血必净干预后可明显降低脾组织Fas、Bax表达,提高IL-2水平,同时可降低IL-10水平,减轻重要脏器的病理损伤。结论血必净干预可通过降低促凋亡相关蛋白表达缓解脓毒症时的免疫麻痹状态。     

脓毒症大鼠肠道肠三叶因子mRNA表达的变化

目的：探讨脓毒症大鼠肠道肠三叶因子（trefoil factor family,TFF3）mRNA表达的变化。方法：32只SD大鼠随机分为对照组（n=8）和脓毒症组（n=24）。采用盲肠结扎穿孔术（cecal ligation and puncture,CLP）制作大鼠脓毒症模型。于模型建立后3h,6h及12h（n=8）取回肠黏膜,以RT-PCR法检测TFF3 mRNA的表达。结果：脓毒症模型建立3h始TFF3 mRNA表达即显著下降（P〈0.01）,随着时间延长表达进一步下降。结论：脓毒症大鼠肠道TFF3 mRNA表达明显下降,可能是脓毒症肠屏障功能障碍的机制之一并延缓肠道黏膜修复。     

影响脓毒症受损肠黏膜修复的机制

目的 探讨影响脓毒症肠黏膜损害后修复的因素。方法 采用肓肠结扎穿孔(CLP)所致脓毒症模型,分别以CLP后6,24,48 h不同时间段观测肠黏膜损伤程度和修复过程,前者包括形态学观察及细胞凋亡的测定,后者包括肠黏膜修复的杯状细胞变化、黏膜肠三叶因子3(TFF3)、转化生长因子β1(TGF-β1)以及TNF-α、IL-1含量。结果 形态学观察显示肠黏膜呈持续损害状态,6h的损害积分明显小于24h,48 h组(P＜0.05),后两组之间差异无统计学意义(P＞0.05);磷酸化caspase-3蛋白在3组均高于sham组4倍以上;黏膜IL-1,TNF-α含量明显高于sham组3～4倍,其中24h及48 h组明显高于6h组。肠黏膜的修复过程不明显,损伤黏膜未见到明显的杯状细胞积聚;TFF3在6h组轻度增高,24h及48 h组表达下降;杯状细胞数量在CLP的3个组明显减少;TGF-β1在6h组增高,其他两组均接近于sham组。结论 严重脓毒症肠黏膜持续的高炎症状态、杯状细胞功能以及黏膜重建能力下降,影响了受损肠屏障的修复。     

Repair of damaged intestinal mucosa in a mouse model of sepsis

BACKGROUND:

The intestine is not only the main target attacked by sepsis but also the vital organ which mediated sepsis. The recovery of the damaged intestinal barrier structure and function is related to the occurrence and outcome of multiple organ dysfunction syndrome (MODS). How to protect and reduce the damage of the intestinal mucosa and how to promote the reconstruction of the intestinal mucosa have been the important topics in sepsis for many years. This study aimed to investigate the influential factors of intestinal mucosal reconstruction after intestinal epithelial injury in vivo in a mouse model of sepsis.

METHODS:

Mice were subjected to cecal ligation and puncture (CLP) for induction of sepsis to assess intestinal mucosal damage, epithelial cell apoptosis, and transformed number of goblet cells, and to detect the concentration of TNF-α, IL-1 and TGF-β1 and TFF3 (trefoil factor 3) expression in the small intestinal mucosa. All above were performed by HE staining, western blot, ELISA and immunohistochemistry respectively. The experimental animals were divided into a sepsis group and a sham-operation group. The animals with sepsis were separately killed at 6 (7 animals), 24 (7 animals) and 48 hours (7 animals) after CLP.

RESULTS:

Injured intestinal mucosa was observed in the 3 groups under a light microscope, in which damage scores in the 24-hour and 48-hour groups were higher than in the 6-hour group and no difference was found between the two groups. Moreover, less of goblet cells or other epithelial cells adjacent to the injured surface migrated into the wound to cover the denuded area. The number of goblet cells was substantially decreased in the three CLP groups compared with the sham-operation group. Protein levels of IL-1 and TNF-α were significantly increased by 3–4 fold at all time points when compared with the sham-operation group, and cleaved caspase-3 by 4 fold. Although TFF3 expression was modestly increased for 6 hours after the onset of CLP, it appeared to decline at 24 hours and 48 hours as shown by Western blot. A similar tendency was observed upon TGF-β1, i.e. the protein level was not elevated at 24 hours and 48 hours, but increased modestly at 6 hours.

CONCLUSIONS:

Sepsis from CLP shows less restitution on the surface of injured intestinal mucosa. There is evidence that both constant inflammatory reaction and epithelial cell apoptosis may affect mucosal reestablishment of the intestine at the onset of sepsis. Mucosa after severe sepsis showed the state of high inflammation, and declined goblet cell function and mucosal reconstruction, which affected the repair of damaged intestinal barrier. Constant inflammatory reaction, and declined goblet cell function and mucosal reconstruction ability may affect the reestablishment of intestinal mucosa at the onset of sepsis.KEY WORDS: Sepsis, Cecal ligation and puncture, Intestinal mucosa, Restitution, Goblet cells, Intestinal trefoil factor 3, Transforming growth factor β1, Cysteine-containing aspartate-specific proteases     

Influence of cyclooxygenase inhibitors on gut immune cell distribution and apoptosis rate in experimental sepsis

The aim of this study was to determine if cyclooxygenase (COX) inhibitors influence immune cell distribution in the small intestinal mucosa and mesenteric lymph nodes (MLNs), the grade of mucosal damage, and the rate of apoptosis in septic rats. The effects induced by a selective COX-2 inhibitor (SC-236) were compared with those of a nonselective COX-1 and -2 inhibitor (indomethacin). Cecal ligation and puncture (CLP), CLP + SC-236 p.o, and CLP + indomethacin p.o, were evaluated. Animals were harvested 6 and 24 h after CLP, respectively. The concentration of proinflammatory cytokines was higher in ascitic fluid than in blood. CLP + SC-236 attenuated IL-6 in plasma and in ascitic fluid and CLP + indomethacin augmented TNF-alpha in ascitic fluid compared with CLP at 6 h. CLP + SC-236 gave a lesser degree of mucosal damage compared with CLP alone or with indomethacin at 6 and 24 h (P < 0.05). Untreated CLP had significant reductions in the number of T lymphocytes in the villi and increases of macrophages in the mucosa and MLNs compared with controls (P < 0.05). CLP + indomethacin decreased T lymphocytes in the villi and MLNs. CLP caused an enhanced apoptosis in the mucosa compared with controls (P < 0.05), pretreatment with COX inhibitors did not significantly change this. Both COX inhibitors enhanced apoptosis in MLNs and attenuated the increase of macrophages in mucosa and MLNs (P < 0.05). It is proposed that the increased apoptosis and the decrease in T cells in the mucosa may be causally related. Apoptosis of lymphocytes may impair the immunologic defense in sepsis. Furthermore, loss of intestinal epithelial cells may compromise bowel wall integrity and facilitate translocation.     

乌司他丁对脓毒症大鼠肠道防御素5 mRNA表达的影响

目的 探讨乌司他丁(ulinastatin,LTI)对脓毒症大鼠肠道潘氏细胞防御素5(rat defemin-5,RD-5)mRNA表达的影响.方法 实验在中山大学医学院药理实验室完成.60只SD大鼠随机分为对照组、脓毒症组、预处理组及治疗组(n=15).后三组采用盲肠结扎穿孔术(cecal ligation andpuncture,CLP)制作大鼠脓毒症模型.预处理组在CLP前2h经尾静脉注射UTI 25 000 U/kg,治疗组在CLP后2 h经尾静脉注射UTI 50 000 U/kg.于模犁建立后12 h取回肠黏膜,观察其病理改变并以RT-PCR法检测RD-5 mRNA的表达.数据以SPSS 13.0统计软件处理,采用方差分析及LSD-t检验进行数据分析.结果 RD-5 mRNA在脓毒症组显著下降(P<0.05),预处理组及治疗组较脓毒症组有明显升高(P<0.05),预处理组较治疗组明显升高(P<0.05).结论 脓毒症大鼠RD-5mRNA表达明显下降,乌司他丁可显著上调其表达,保护肠黏膜,预防用药较治疗给药可能更有意义.     

血必净注射液对脓毒症大鼠蛋白C及肿瘤坏死因子基因表达的影响

目的探讨血必净注射液对脓毒症大鼠蛋白C（PC）及肿瘤坏死因子-α（TNF—α）基因表达的影响。方法将96只健康Wistar大鼠按随机数字表法分为正常对照组、假手术组、模型组和血必净治疗组，后两组又按处死时间分为术后2、8、24、48和72h亚组，每组8只。采用盲肠结扎穿孔术（CLP）制备脓毒症模型。取腹主动脉血进行血小板计数，并留取肝、肺组织分别检测各组动物组织PC和TNF—α的mRNA表达。结果CLP后8～72h模型组大鼠肝组织PC mRNA表达显著下调（P均〈0．01），血必净注射液可显著提高脓毒症大鼠PC mRNA表达水平（P均〈0．01）。CLP后2h模型组动物肝、肺组织TNF—α mRNA表达均迅速升高并持续至伤后24h（P〈0．05或P〈0．01）；血必净注射液治疗可显著降低肝、肺组织TNF—α mRNA水平（P〈0．05或P〈0．01），术后24h均恢复至伤前正常范围。模型组动物CLP后8～72h血小板计数不同程度减少，血必净治疗组较模型组能明显提高血小板计数（P〈0．05或P〈0．01）。结论血必净注射液可以从基因水平影响脓毒症动物组织PC和TNF—α的mRNA表达。     

Effect of L-Arginine on intestinal mucosal injury of rats with severe abdominal infection]

OBJECTIVE: To investigate the effect of L-Arginine on intestinal mucosal injury of rats with severe abdominal infection. METHODS: Rats received cecal ligation and puncture (CLP) to reproduce sepsis model. A total of 18 Wistar rats were divided into two groups randomly (each n=9): L-Arginine group and model group. Three hundred mg/kg of L-Arginine was injected into the abdomen in rats of L- Arginine group after CLP. Model group received equal volume of normal saline. Blood sample was harvested and the serum levels of nitric oxide (NO) and inducible nitric oxide synthase (iNOS) were determined at 24 hours after operation in both groups. The histopathological change of intestinal mucosa was observed under light microscope and mucosa damage index was determined. RESULTS: The intestinal mucosal damage was observed both in model group and L- Arginine group after CLP, but the injury was milder in L- Arginine group. There was significant difference in mucosa injury index between L-Arginine group and model group (3.4+/-0.6 vs. 4.1+/-0.5, P<0.05). The serum level of NO [(76.1+/-26.2) micromol/L vs. (87.3+/-16.7) micromol/L, P>0.05] and iNOS [(30.6+/-7.4) U/L vs(44.4+/-6.6) U/L, P<0.01] in L-Arginine group were lower than those in model group. CONCLUSION: L-Arginine could protect against intestinal mucosal injury and depress the serum level of iNOS in severe abdominal infection of rats.