卡巴胆碱对烧创伤后肠道功能障碍影响的研究

目的观察肠道内给予卡巴胆碱对兔肠部分缺血再灌注(I/R)损伤及重度烧伤患者肠道功能障碍的影响。方法将50只大白兔制成肠部分I/R损伤模型后,随机分为肠部分I/R损伤组(25只)、卡巴胆碱组[25只,于肠系膜上动脉(SMA)阻断后1h肠内注入3g/L卡巴胆碱(3μg/kg)]；另取25只设为假手术组,仅分离SMA,不阻断；取5只作为正常对照组,不致伤,处死后留取标本待测。检测兔SMA阻断前后及肠道内给予卡巴胆碱后肠黏膜的血流量。各致伤组均在处理后2、4、6、8、24、48、72h留取静脉血测定其血浆二胺氧化酶(DAO)活性及D-乳酸和D-木糖含量。并行葡聚糖蓝排出实验,以检测胃肠道吸收功能。同时选择大面积烧伤[烧伤总面积(84±12)%TBSA]患者8例,在患者肠呜音＜2次/min或腹胀明显时,口服1g/L卡巴胆碱(15μg/kg),观察给药后每分钟肠鸣音次数及腹胀情况。结果SMA阻断后肠部分I/R损伤组肠黏膜血流量为(48±6)PU,较正常对照组[(102±5)PU]明显减少,而肠道内注入卡巴胆碱后1h血流量增至(77±3)PU。肠缺血后肠部分I/R损伤组血浆DAO活性及D-乳酸含量开始升高,处理后24h达峰值[(4．63±0．27)U/ml、(7．9±2．4)mg/L],以后逐渐下降,但仍高于正常对照组[(0．89±0．14)U/ml、(2．0±1．1)mg/L,P＜0．05]。卡巴胆碱组的变化基本同肠部分I/R损伤组,但变化幅度较小；而假手术组则无明显变化(P＞0．05)。在给予D-木糖后2h,肠部分I/R损伤组血浆D-木糖含量显著降低,但处理后6h肠部分I/R损伤组及卡巴胆碱组明显升高,以后逐渐下降；假手术组略有波动。SMA处理后2h肠部分I/R损伤组葡聚糖蓝未见排出,处理后6h其运动距离逐渐增加,但处理后24h其运动距离仍明显短于正常值(P＜0．05),48～72h基本恢复正常；卡巴胆碱组注入葡聚糖蓝后即可见其排出,其运动距离明显增加,处理后6h达峰值(43±6)cm,以后逐渐缩短接近正常(28±3)cm。给药前患者肠呜音较弱(1．6±1．1)次/min,给药后10 min明显增强为(6．9±1．7)次/min,30 min时为(8．3±2．4)次/min,给药后1h患者肠鸣音仍较活跃,为(6．1±1．3)次/min。给药后2h患者腹胀明显减轻,其中有6例患者开始排便。结论肠内给予卡巴胆碱可增加兔肠黏膜血流量,改善其肠道运动、吸收、屏障功能；大面积烧伤患者口服卡巴胆碱,可改善其肠道功能障碍。     

卡巴胆碱对肠缺血/再灌注大鼠中性粒细胞CD11b/CD18表达和血清可溶性细胞间黏附分子-1浓度的影响

目的:观察胆碱能激动剂卡巴胆碱对肠缺血/再灌注大鼠中性粒细胞(PMN)上CD11b/CD18表达和血清可溶性细胞间黏附分子-1(sICAM-1)浓度的调节作用。方法:54只雄性Wistar大鼠随机分为假手术组(N组)、肠缺血/再灌注组(GI/R组)及卡巴胆碱干预组(Car组)。采用夹闭肠系膜上动脉45min后恢复灌流的方法制成GI/R模型;卡巴胆碱组在肠缺血15min后经幽门注入卡巴胆碱(100μg/kg)。于肠缺血45min(I45)及再灌注1h(R1)、2h(R2)、6h(R6)取肠系膜上静脉血,双抗体夹心酶联免疫吸附(ELISA)法测定血清sICAM-1浓度,流式细胞仪检测PMN上CD11b/CD18表达率。结果:肠系膜上静脉血中PMN表面黏附分子CD11b/CD18的表达在肠缺血和再灌注后各时相点均增加(P<0.01),R2和R6时增加幅度较大;卡巴胆碱干预组R6时CD11b/CD18阳性PMN比例减少(P<0.05)。血清sICAM-1浓度在R1～R6时均升高(P<0.05),而给予卡巴胆碱的动物R6时降低(P<0.05),其值接近N组。结论:卡巴胆碱能降低肠缺血/再灌注大鼠PMN上CD11b/ C...     

HMGB1 A box蛋白对于急性胰腺炎脏器损伤的保护作用

目的 应用高迁移率族蛋白-1(HMGB1)的拮抗剂-A box蛋白治疗小鼠急性胰腺炎模型并观察其疗效.探讨A box蛋白对于急性胰腺炎所致脏器损伤影响的作用机制.方法 以20%L-精氨酸腹腔注射诱导建立小鼠急性坏死性胰腺炎模型,并于建模后应用A box蛋白进行治疗,测定血AST、ALT、LDH、BUN及Cr等生化指标.比较对照组和治疗组小鼠的胰腺、肺、肾、肝的病理变化及两组小鼠的存活率和存活时间.结果 建模后48 h,治疗组小鼠的胰腺、肺组织损伤病理评分较对照组减少,有显著性差异(P<0.05),治疗组肾、肝组织损伤的病变程度较对照组减轻.建模后24 h治疗组的AST值较对照组明显降低(P<0.05),建模后48 h治疗组的AST、ALT、LDH和Cr值较对照组明显降低(P<0.05).治疗组小鼠的存活率(66.7%)明显高于对照组的存活率(26.7%)(P<0.05).结论 A box蛋白对于胰腺炎及其所引发的肺、肾、肝等脏器的损伤有显著的保护作用.可提高重症胰腺炎小鼠的存活率.     

卡巴胆碱对烫伤休克大鼠肺血管通透性影响的初步研究

目的:研究烫伤休克大鼠液体复苏时给予卡巴胆碱对肺血管通透性和含水量的影响.方法:78只Wistar大鼠随机分为3组:烫伤组(n=36),卡巴胆碱治疗组(n=36)和正常组(n=6).采用30%TBSA Ⅲ度烫伤模型,应用改良伊文思蓝渗出法测定伤前及伤后4、8和12 h(n=6)肺组织血管通透性及肺含水量的变化.结果:伤后4 h卡巴胆碱治疗组伊文思蓝含量为(45.11±4.19)μg/g,较烫伤组(75.18±3.80)μg/g明显降低(P＜0.01),而与正常组(42.51±5.07)μg/g比较无统计学差异;伤后4 h、8 h卡巴胆碱治疗组的肺含水量显著低于烫伤组[(76.03±1.70)%比(78.46±1.42)%,(76.57±1.27)%比(80.15±1.84)%,P＜0.05和P＜0.01];伤后12 h肺组织血管通透性及含水量与烫伤组比较均无统计学差异.结论:卡巴胆碱能降低烧伤早期肺血管通透性及含水量增加,有助于烧伤休克早期的治疗.     

卡巴胆碱改善重度烫伤大鼠胃血流量和胃排空功能的初步研究

目的:探讨不同剂量卡巴胆碱对烫伤大鼠胃血流量和胃排空功能的影响.方法:40只Wistar雄性大鼠,随机分为假烫组(n=5)、单烫组(n=5)和口服卡巴胆碱组(n=30),后者又根据卡巴胆碱剂量不同分为20、40、60、80、100、120 μg/kg组(每组5只).假烫组大鼠均给予0.1%酚红溶液1.5 ml灌胃.单烫组和口服卡巴胆碱组大鼠均经30%TBSAⅢ度烫伤后立即给予0.1%酚红溶液1.5 ml灌胃,口服卡巴胆碱组于伤后0.5 h给予相应剂量卡巴胆碱 1 ml生理盐水灌胃.大鼠均于伤后2 h处死,观察不同剂量卡巴胆碱对大鼠胃血流量及胃排空率的影响.结果:烫伤后大鼠胃排空率为(29.50±13.42)%,明显低于假烫组(92.19±5.24)%,P＜0.01.伤后2 h胃血流量从伤前的(476.00±71.24)U降低到(103.60±51.28)U,P＜0.01.烫伤后给予不同剂量卡巴胆碱均能增加胃排空率和胃血流量,但以60 μg/kg最为显著(P＜0.01).结论:卡巴胆碱对烧伤休克大鼠胃血流量和胃排空有显著促进作用,最佳剂量为60μg/kg.     

Toll样受体4在失血性休克复苏致小鼠急性肺损伤中的作用

目的 探讨Toll样受体4(TLR4)在失血性休克复苏致小鼠急性肺损伤中的作用.方法 TLR4基因突变型C3H/HeJ小鼠和野生型C3H/HeN小鼠各24只,两种品系小鼠各随机分为2组:假手术组(S组,n=6)、失血性休克复苏组(HSR组,n=18)制备失血性休克复苏模型,并于复苏后6、24、48 h时各取6只小鼠颈动脉放血处死后开胸取肺组织,免疫组织化学法检测p38 MAPK表达水平,酶联免疫吸附法测定白细胞介素(IL)-10和IL-6含量,透射电镜下观察肺组织超微结构.结果 与C3H/HeN小鼠比较,C3H/HeJ小鼠复苏后肺组织p38 MAPK表达下调,IL-6和IL-10含量降低(P<0.05或0.01),病理损伤程度减轻.两种品系小鼠中,与S组比较,HSR组复苏后24 h时肺组织IL-6和IL-10含量增加,复苏后48 h时肺组织IL-6含量增加(P<0.05或0.01);C3H/HeN小鼠中,与S组比较,HSR组复苏后6 h和24 h时肺组织p38 MAPK蛋白表达上调,复苏后48 h时肺组织IL-10含量增加(P<0.01).结论 TLR4参与小鼠失血性休克复苏致急性肺损伤的发生,其机制与激活p38 MAPK信号转导通路有关.     

脓毒症大鼠血清肝肾功及心肌酶谱的变化及意义

目的观察脓毒症大鼠血清谷丙转氨酶(ALT)、尿素氮(BUN)、肌酐(Cr)、肌酸激酶(CK)和乳酸脱氢酶(LDH)的变化特点并探讨其意义。方法雄性SD大鼠36只,随机分为假手术组(n=9)和盲肠穿刺结扎(CLP)组(n=27),CLP组根据术后取材时间不同分为6、12和24 h 3个亚组(n=9)。假手术组仅翻动盲肠,CLP组以CLP术制作脓毒症模型,于造模后6 h、12 h及24 h处死大鼠,取血清标本,检测血清ALT、BUN、Cr、CK和LDH水平。结果与假手术组比较,大鼠血清ALT、BUN、Cr、CK及LDH水平变化均随时间延长逐渐升高,12 h时均达到最高水平,24 h时均开始下降,但仍高于假手术组(P0.05)。结论脓毒症大鼠血清中ALT、BUN、Cr、CK和LDH随时间依赖性改变,与脓毒症的病情严重程度密切相关,提示CLP术后大鼠肝、心、肾功能逐渐受损,12 h功能障碍最显著,12 h后器官可能已发生不可逆病变。     

抗炎灵对大肠杆菌性腹膜炎致多脏器功能不全大鼠模型的防治作用研究

目的：观察抗炎灵（KYL）对大肠杆菌性腹膜炎致多脏器功能不全（MODS）大鼠模型的防治作用，探讨其机制。方法：通过腹腔注射大肠杆菌对大鼠进行多脏器功能不全造模，预防组及治疗组分别于造模前后经口投予KYL；观察大鼠死亡率，测定血清AST、ALT、BUN、Cr、TNF、IL－1和IL－6水平。结果：预防组及治疗组各项观察指标均明显低于模型组。结论：KYL对多脏器功能不全大鼠模型的防治效果显著，其机制是平衡机体炎症与抗炎因子水平。     

52例重症闭合性腹外伤分析

目的 :探讨重症闭合性腹外伤的最佳救治措施。方法 :对 5 2例重症闭合性腹外伤的致伤原因、损伤情况、治疗方法 ,术后并发症及死亡率进行统计分析。结果 :治愈 46例 ,死亡 6例 ,死亡率 11.5 %。主要死亡原因为多脏器功能衰竭 (MODS) ,不可逆性休克 ,急性呼吸窘迫综合症 (ARDS)。结论 :快速有效的现场抢救 ,积极补液抗休克 ,腹内脏器损伤早期诊断 ,正确有序的手术探查 ,术后并发症的早期防治可提高治成功率     

卡巴胆碱对犬烧伤休克早期口服补液效果的影响

目的 观察卡巴胆碱对50%总体表面积(TBSA)Ⅲ度烧伤早期口服补液效果的影响.方法 Beagle犬17条,先期行颈动、静脉、胃及膀胱置管,24 h后用凝固汽油燃烧造成50%TBSAⅢ度烧伤.随机分为不补液组、胃内补液组和胃内补液+卡巴胆碱组.伤后第1个24 h不补液组无治疗,其余2组于伤后30 min开始经胃内输注葡萄糖-电解质液或葡萄糖-电解质液复合卡巴胆碱(20 μg/kg).第1个24 h补液量为4 ml·kg~(-1)·%TBSA~(-1);伤后24 h起各组动物均实施静脉补液,至72 h处死动物.测定两胃内补液组伤后8 h内胃排空率,各组72 h内平均动脉压(MAP)、心输出量(CO)、尿量、血浆肿瘤坏死因子(TNF)-α含量以及伤后72 h脏器组织一氧化氮合酶(NOS)活性变化.结果 伤后3组MAP、CO、尿量及胃排空率均显著降低,血浆TNF-α含量显著增高.两胃内补液组MAP和CO高于不补液组;胃内补液+CAR组CO和胃排空率伤后4 h起显著高于胃内补液组(P<0.01),伤后24 h尿量也显著多于胃内补液组,伤后2、4和8 h血浆TNF-α含量以及伤后72h心、肝和空肠组织NOS活性显著低于胃内补液组(P<0.01或P<0.05).结论 卡巴胆碱能提高50%TBSA烧伤早期口服补液的复苏效果,其作用机制可能与促进胃排空和减轻炎症反应有关.     

The effects of selective nitric oxide synthase blocker on survival, mesenteric blood flow and multiple organ failure induced by zymosan

BACKGROUND: Circulatory failure in multiple organ dysfunction syndromes (MODS) is characterized with systemic vasodilation, diminished blood flow to various vascular beds. The aim of this study was to investigate the effects of selective inhibition of nitric oxide on the mesenteric arterial blood flow (MABF), survival and organ injury of the liver, kidney, lung and spleen in zymosan-induced MODS. MATERIALS AND METHODS: Forty Swiss albino mice (20-40 g), 7 to 9 weeks old, were obtained. Animals were randomly divided into four groups. The first group were treated intraperitoneally (i.p) with vehicle (saline) and served as a sham group for aminoguanidine (AG) (n=10). The second group was treated with zymosan (500 mg/kg, suspended in saline solution, i.p). The mice in the third and fourth group received AG (15 mg/kg) 1 h and 6 h after zymosan or saline administration, respectively. Eighteen hours after the administration of zymosan, animals were assessed for MODS described subsequently. The signals from the flowmeter were also recorded on mesenteric arterial blood flow values. RESULTS: In zymosan-treated animals, the MABF was significantly lower than that of solvent (saline)-treated controls (ml min(-1), controls: 4.6 +/- 0.6; zymosan: 1.6 +/- 0.9, P <0.05). When animals were treated with AG, there were no significant differences in MABF values between AG group and solvent (saline)-treated control group. However AG prevented zymosan-induced mesenteric MABF decrease. Treatment with aminoguanidine also decreased mortality. CONCLUSION: AG is capable of inhibiting both the induction and the activity of the already iNOS; it remains a potential therapeutic agent in patients with MODS.     

胸部开放伤后海水浸泡致多器官功能障碍综合征

目的 探讨实验动物胸部开放伤后海水浸泡致多器官功能障碍（ＭＯＤＳ）的发生率和发生特点。方法 成年杂种犬致伤后随机分为对照组（单纯胸伤组,ｎ＝１０）和实验组（ｎ＝１０）。实验组动物于伤后置入人工配制的海水中。实验过程中动态监测血清丙氨酸氨基转移酶（ＡＬＴ）、门冬氨酸氨基转移酶（ＡＳＴ）、肌酸肌酶（ＣＫ）、乳酸脱氢酶（ＬＤＨ）、尿素氮（ＢＵＮ）和肌酐（Ｃｒ）以及肿瘤坏死因子α（ＴＮＦα）和白细胞介素１     

Relationship between HMGB1 content and MHC-Ⅱ expression in circulating monocytes and spleen of mice challenged with zymosan

Objective: To observe the regularity of change in high mobility group protein box 1 (HMGB1) content in serum and spleen of mice with multiple organ dysfunction syndrome (MODS), to analyze the correlation between HMGB1 content and major histocompatibility complex (MHC)-Ⅱ-I-Ab expression on monocytes in blood and spleen, and to explore the effect of HMGB1 on immune function of circulating monocytes and splenocytes. Methods: One hundred 8-week-old male 57BL/6 mice were randomly divided into normal group and experimental group subdivided into 8 subgroups: 3, 8, 12 hours, 1, 2, 3, 5-7 days and 10-12 days post zymosan injection (PZI). MODS model was replicated by injecting zymosan into the peritoneal cavity. At each time point, blood and spleen were collected to detect HMGB1 content and the rate of I-Ab positive monocytes. Results: In normal and PZI 3-hour, 8-hour mice, serum HMGB1 was not detected, but it significantly increased at PZI 12 hours. In spleen of normal mice, there was low level of HMGB1 expression. In zymosan-treated mice, HMGB1 started to rise in spleen at PZI 3 hours. Subsequently, HMGB1 content in both serum and spleen significantly increased, and it reached the peak level in 1-2 days, decreased in 5 days, and then increased in 10-12 days. The number of I-Ab positive monocytes in circulating blood and spleen decreased at 1-2 days (t=9.589, 4.432, P<0.01) and 10-12 days following the challenge, forming a two trough like decrease, just corresponding with two-peak increase of HMGB1. However, at 3 hours after zyrnosan challenge, I-Ab expression on circulating monocytes was downregulated (t=5.977, P<0.01), while that in spleen upregulated (t=4.814, P<0.01). Conclusion: In mice with MODS, up-regulated HMGB1 expression can regulate I-Ab expression on monocytes to depress their ability of presenting antigen, which results in immune disturbance contributing development of MODS.     

连续性血液透析滤过对多器官功能障碍犬器官功能和细胞因子的影响

观察连续性血液透析滤过（CVVHDF）对多器官功能障碍综合征(MODS)犬器官功能和细胞因子的影响，并探讨CVVHDF治疗MODS的机制。 方法 15只Beagle犬采用失血性休克+复苏灌注+内毒素血症复制MODS模型，随机分为CVVHDF组(n=8)和MODS组(n=7)。内毒素注射完毕后CVVHDF组接受CVVHDF治疗12 h；MODS组未接受CVVHDF治疗。检测各时间点动脉血氧分压(PaO2)、动脉血二氧化碳分压(PaCO2)、谷丙转氨酶（ALT）、谷草转氨酶（AST）、Scr、BUN的水平。ELISA检测血浆TNF-α、IL-6、IL-10浓度。 结果 CVVHDF治疗后血浆IL-6、IL-10显著下降, 在3、6、9及12 h时间点显著低于MODS组，差异均有统计学意义（P < 0.01）；血浆TNF-α浓度无明显变化，两组间各时间点差异无统计学意义。超滤液中检出IL-6、TNF-α，筛选系数分别为0.27±0.13、0.1±0.1，但未能检出IL-10。CVVHDF组各主要器官功能均明显改善, 平均动脉压基本保持在正常水平，尤其在6、9及12 h时间点显著高于MODS组，差异均有统计学意义（P < 0.01）。PaO2逐渐升高，与MODS组在3、6、9及12 h时间点比较，差异均有统计学意义（P < 0.01）。 结论 连续性血液透析滤过能有效降低血浆IL-6、IL-10水平,使抗炎反应和促炎反应两方面趋于动态平衡；能明显改善内毒素诱导的低血压，提高动脉血氧分压。     

严重创伤患者白细胞介素—2及其受体变化与多器官功能障碍综合 …

目的 探讨血清白介素－２（ＩＬ－２）与可溶性白介素－２受体（ｓＩＬ－２Ｒ）在创伤后多器官功能障碍综合征（ＭＯＤＳ）发生、发展中的作用机制。方法 应用ＥＬＩＳＡ法动态监测５９例严重创伤患者血清ＩＬ－２与ｓＩＬ－２Ｒ水平变化,比较ＭＯＤＳ与非ＭＯＤＳ组间ＩＬ－２、ｓＩＬ－２Ｒ变化之差异。结果 ５９例患者血甭ｓＩＬ－２Ｒ水平显著升颃是ＩＬ－２明显下降,且升 峰值与降低之谷值在ＭＯＤＳ组更为明显,与非ＭＯ     

Altered chemokine response in an animal model of multiple organ dysfunction syndrome induced by zymosan

Purpose

The aim of this study was to determine the monocyte chemoattractant protein-1 (MCP-1) response over time in an animal model of multiple organ dysfunction syndrome (MODS).

Methods

On day 0, rats were randomized to receive an intraperitoneal injection of zymosan at a dose of 1 mg/g of body weight (n = 36) or vehicle (n = 9). Serum, peritoneal lavage (PL) fluid, and bronchoalveolar lavage (BAL) fluid were collected from 3 rats in the control group and 6 to 7 rats in the zymosan group at days 1, 5, and 12. Monocyte chemoattractant protein-1 concentrations were determined by enzyme-linked immunosorbent assay.

Results

The authors observed a 47% mortality in the zymosan-treated rats. Monocyte chemoattractant protein-1 levels were unchanged in the serum, PL, and BAL of control animals. Both serum and PL MCP-1 were significantly higher in zymosan-treated rats on days 1 (P < .01) and 5 (P < .05) when compared with controls. By day 12, no difference between the 2 groups was observed. No significant difference was noted in BAL MCP-1.

Conclusions

Chemokines are increased systemically and locally during MODS. The fact that MCP-1 is significantly higher early in the course of MODS may suggest that this chemokine is important in the early inflammatory changes that lead to MODS later in the course of this illness.     

连续性血液透析滤过对MODS犬肝肾IL-6和IL-10 mRNA表达的影响

目的：探讨连续性血液透析滤过（CVVHDF）后多器官功能障碍综合征（MODS）犬肝、肾组织白细胞介素-6（IL-6）和白细胞介素-10（IL-10）mRNA表达水平的变化及意义。方法：15只雄性Beagle犬,采用失血性休克＋复苏灌注＋内毒素血症复制MODS模型,随机分为CVVHDF组（n=8）和MODS组（n=7）,CVVHDF组在内毒素注射完毕后给予CVVHDF治疗12h,MODS组不给CVVHDF治疗。测定各器官功能相关指标,同时应用半定量逆转录-聚合酶链反应（RT-PCR）测定两组肝、肾组织中IL-6、IL-10mRNA表达水平。结果：CVVHDF组治疗后肝、肾功能有关指标水平均有不同程度的改善;与MODS组相比,在内毒素注射后3h及以后各时间点,血清肌酐（Scr）、尿素氮（BUN）水平显著降低（P〈0.05）;器官衰竭发生率较MODS组明显降低（37.5%vs85.7%,P〈0.05）;MODS组肝、肾组织IL-6mRNA表达水平显著高于正常对照组和CVVHDF组（P〈0.01）,而CVVHDF组肝、肾组织IL-10 mRNA表达水平显著高于正常对照组和MODS组（P〈0.01）。结论：连续性血液透析滤过能明显改善肾功能,CVVHDF早期应用可以降低MODS肝、肾组织IL-6/IL-10mRNA比值,有助于重建机体免疫系统内稳状态。     

严重创伤患者白细胞介素-2及其受体变化与多器官功能障碍综合征的关系

目的　探讨血清白介素２（ Ｉ Ｌ２） 与可溶性白介素２ 受体（ｓ Ｉ Ｌ２ Ｒ） 在创伤后多器官功能障碍综合征（ Ｍ Ｏ Ｄ Ｓ） 发生、发展中的作用与机制。　方法　应用 Ｅ Ｌ Ｉ Ｓ Ａ 法动态监测５９ 例严重创伤患者血清 Ｉ Ｌ２ 与ｓ Ｉ Ｌ２ Ｒ 水平变化,比较 Ｍ Ｏ Ｄ Ｓ与非 Ｍ Ｏ Ｄ Ｓ组间 Ｉ Ｌ２ 、ｓ Ｉ Ｌ２ Ｒ 变化之差异。　结果　５９ 例患者血清ｓ Ｉ Ｌ２ Ｒ 水平显著升高而 Ｉ Ｌ２ 明显下降,且升高之峰值与降低之谷值在 Ｍ Ｏ Ｄ Ｓ组更为明显,与非 Ｍ Ｏ Ｄ Ｓ组间差异显著（ Ｐ＜ ００５） 。　结论　 Ｉ Ｌ２ 与ｓ Ｉ Ｌ２ Ｒ 血清浓度的变化可能参与了创伤后 Ｍ Ｏ Ｄ Ｓ的发病过程;严重创伤诱发血清ｓ Ｉ Ｌ２ Ｒ 过度表达进而抑制 Ｉ Ｌ２ 依赖性免疫反应,这可能是创伤后 Ｍ Ｏ Ｄ Ｓ重要发病机制之一。     

Effect of high volume hemofiltration on CHOP protein from a canine model of multiple organ dysfunction syndrome

Objective To observe the effect of high volume hemofiltration (HVHF) on the expression of CCAAT enhancer binding protein(CHOP) during the treatment of multiple organ dysfunction syndrome (MODS). To investigate the role of CHOP protein act in apoptosis pathway mediated by the endoplasmic reticulum stress. Methods Twelve Beagle dogs were subjected to hemorrhagic shock plus resuscltation and endotixemia to establish MODS model, then they were randomly divided into two groups: HVHF group (n=6) and MODS group (n=6). After endotoxin injection completed, the HVHF group received HVHF treatment for 24 hours; MODS group did not receive. Vivo experiments: Blood samples were obtained at different time points(before operation, 0 h, 6 h, 12 h, 24 h after the injection of endotoxin). The dogs were killed and the tissue samples from lung, liver and kidney were took, then the expression of CHOP mRNA was determined. Vitro experiments: human umbilical vein endothelial cells (HUVECs) were induced by two groups’ blood samples to establish the apoptosis model. Gene expression, protein quantification and cell apoptosis rate were determined before and after the interference. Results Vivo experiments: The levels of CHOP mRNA from lung, liver and kidney had no significant difference between the two groups (P＞0.05). Vitro experiments: (1)The expression of CHOP mRNA: Compared with MODS group, the expression levels of CHOP mRNA were significantly decreased in HVHF group at 6 h, 24 h after the injection of endotoxin (P＜0.05). Compared with before, the expression levels of CHOP mRNA in the two groups were both significantly decreased after CHOP siRNA interference (P＜0.05). (2)The expression of CHOP protein: Compared with MODS group, the expression levels of CHOP protein were significantly decreased in HVHF group at each time points (P＜0.05). Compared with before, the expression levels of CHOP protein in the two groups were both significantly decreased after CHOP siRNA interference(P＜0.05). (3)Endothelial cell apoptosis rate: Compared with the preoperative rate, the two group’s endothelial cell apoptosis rate was decreased significantly at each time points(P＜0.05). Compared with MODS group, the endothelial cell apoptosis rate was significantly decreased in HVHF group at each time points(P＜0.05). Compared with before, the endothelial cell apoptosis rate in the two groups was both significantly decreased after CHOP siRNA interference(P＜0.05). Conclusion In the treatment of MODS process, HVHF can reduce endothelial cell apoptosis which may be related to the inhibition of CHOP mRNA expression and protein synthesis.