丙泊酚对内毒素性急性肺损伤大鼠血清TNF-α、IL-1β及IL-10的影响

目的探讨内毒素性急性肺损伤(ALI)大鼠用丙泊酚后处理对血清肿瘤坏死因子(TNF)-α、白细胞介素(IL)-1β和IL-10影响。方法雄性SD大鼠96只,随机均分为四组,每组24只。脂多糖(LPS)致伤组(B组)、丙泊酚低剂量治疗组(C组)和丙泊酚高剂量治疗组(D组)经尾静脉注射LPS 5 mg/kg制作ALI模型;之后生理盐水对照组(A组)和B组泵入生理盐水,C、D组分别注射丙泊酚2、4 mg/kg后再分别泵入4、8 mg.kg-1.h-1。分别在制模后1、2、3、4 h抽取动脉血测定TNF-α、IL-1β及IL-10的水平。结果制模后各时点A组大鼠TNF-α、IL-1β和IL-10含量均明显低于其它三组(P<0.05或P<0.01)。制模后1、2 h B组TNF-α、IL-1β和IL-10含量明显高于C、D组(P<0.01),C组IL-1β和IL-10含量明显高于D组(P<0.05或P<0.01)。制模后3、4 h B组IL-1β和IL-10含量仍明显高于C、D组(P<0.01),C组显著高于D组(P<0.01)。结论丙泊酚可以显著抑制ALI大鼠血清TNF-α、IL-1β及IL-10上升的程度。     

抗内毒素Fab'对严重烧伤早期肠道的保护作用

脓毒症是严重烧伤患者最常见的并发症,也是多器官功能障碍综合征(MODS)的主要诱因之一[1].有研究表明肠道在全身性炎症反应综合征(SIRS)、脓毒症、MODS的连续发生发展中起重要作用[2].肠源性脓毒症的防治已成为目前危重病研究的热点.内毒素(LPS)是引起严重创伤和烧伤并发SIRS、脓毒症以及MODS的重要因素之一[3].本研究通过建立小鼠的严重烧伤早期肠源性内毒素血症模型,探讨抗内毒素Fab'对严重烧伤早期肠道损伤的保护作用.     

白细胞介素-10对内毒素血症大鼠肝损伤的影响

目的 评价白细胞介素-10(IL-10)对内毒素血症大鼠肝损伤的影响.方法 清洁级雄性Wistar大鼠100只,10 ～ 14周龄,体重250 ～ 300 g,采用随机数字表法,将其随机分为5组(n=20)∶对照组(C组)、内毒素血症组(LPS组)、1L-10组(IL-10组)、HO-1诱导剂钴原卟啉Ⅸ组(Co组)和HO-1抑制剂锌原卟啉Ⅸ组(Zn组).LPS组、IL-10组、Co组和Zn组腹腔注射脂多糖(LPS) 20 mg/kg,IL-10组、Co组和Zn组于给予LPS前3h腹腔注射重组人IL-10 1 μg,Co组和Zn组分别于给予重组人IL-10后2h腹腔注射钴原卟啉Ⅸ和锌原卟啉Ⅸ25 mg/kg.每组于注射LPS后24 h时取10只大鼠,采集心脏全血,测定血清谷草转氨酶(ALT)、谷丙转氨酶(AST)、肿瘤坏死因子-α(TNF-α)和白细胞介素-1β(IL-1β)的水平;然后取肝组织,测定谷胱甘肽过氧化物酶(GSH-Px)和超氧化物歧化酶(SOD)活性、丙二醛(MDA)含量和血红素氧合酶-1(HO-1)mRNA表达.每组取10只大鼠,记录给予LPS后72 h内大鼠生存情况.结果 与C组比较,LPS组、IL-10组、Co组和Zn组血清ALT、AST、TNF-α、IL-1β水平和肝组织MDA含量升高,肝组织GSH-Px、SOD活性和生存率降低(P＜0.05);与LPS组比较,IL-10组和Co组血清ALT、AST、TNF-α、IL-1β水平和肝组织MDA含量降低,肝组织GSH-Px、SOD活性、HO-1 mRNA表达和生存率升高(P＜0.05);与IL-10组比较,Zn组血清ALT、AST、TNF-α、IL-1β水平和肝组织MDA含量升高,肝组织GSH-Px、SOD活性和生存率降低(P＜0.05),Co组上述指标差异无统计学意义(P＞0.05).结论 IL-10可减轻内毒素血症大鼠肝损伤,其机制与诱导HO-1表达有关.     

异丙酚对内毒素诱导大鼠急性肺损伤的保护作用

目的 探讨不同剂量异丙酚对内毒素(LPS)诱导大鼠急性肺损伤(ALI)的保护作用。方法 股静脉注射内毒素(LPS)5mg/kg,建立大鼠ALI模型。24只健康雄性Wistar大鼠随机分为四组:对照组(C组,输注生理盐水),LPS对照组(L组,股静脉注射LPS后输注生理盐水),低剂量异丙酚治疗组(Lp1组,股静脉注射LPS后立即输注异丙酚5mg/kg,随后5mg·kg~(-1)·h~(-1)维持),高剂量异丙酚治疗组(Lp2组,股静脉注射LPS后立即输注异丙酚10mg/kg,随后10mg·kg~(-1)·h~(-1)维持),每组6只。于注射LPS后1、2、3、4h抽血并于4h时处死大鼠,酶联免疫吸附法(ELISA)测定血清和支气管肺泡灌洗液(BALF)中肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)、白细胞介素-10(IL-10)水平;测肺湿/干重比;并观察BALF中性粒细胞计数比、蛋白浓度。结果 L组大鼠肺湿/干重、BALF中性粒细胞计数比及蛋白浓度均明显增加(P<0.05),血清及BALF中TNF-α、IL-1β、IL-10水平显著性升高(P<0.01),而异丙酚治疗组的各项指标均较内毒素组减轻,大剂量作用更明显(P<0.01)。结论 异丙酚对内毒素诱导的大鼠急性肺损伤有保护作用,大剂量作用较明显。     

乌司他丁影响严重脓毒症大鼠IL-10、TNF-α、IL-1β水平的研究

目的探讨乌司他丁(UTI)对细菌性严重脓毒症大鼠血清IL-10、TNF-α、IL-1β水平的调控作用。方法将SD大鼠随机分为生理盐水对照组、氧氟沙星抗感染组、UTI-氧氟沙星抗炎抗感染组和UTI组。每组15只。经腹腔内注射创伤弧菌建立脓毒症模型,15 h后取单侧颈总动、静脉血标本测定血清IL-10、TNF-α、IL-1β的水平。结果UTI-氧氟沙星抗炎抗感染组较氧氟沙星抗感染组、UTI组及生理盐水对照组的TNF-αI、L-1β水平显著降低(P<0.01),IL-10水平差别无统计学意义(P>0.05)。结论UTI能下调致炎因子TNF-α、IL-1β,并对IL-10有一定的上调作用,从而减轻组织器官炎症反应的病理损害而起保护作用,避免全身炎症反应综合征进一步向MODS发展。     

盐酸戊乙奎醚对正常人离体白细胞炎性介质的影响

目的 通过对正常人离体白细胞促炎和抗炎处理.观察盐酸戊乙奎醚对人离体白细胞炎性介质分泌的影响.方法 严格无菌抽取正常成年人静脉血10 ml,加入淋巴细胞分离液.2 000 r/min离心15 min,取出白细胞,加1 640培养液使白细胞浓度为106个/ml.平均分为五组,每组6个样本.Ⅰ组:对照组;Ⅱ组:加内毒素;Ⅲ组:加盐酸戊乙奎醚后20 min加内毒素;Ⅳ组:加内毒素1 h后加盐酸戊乙奎醚;V组:加阿托品(与盐酸戊乙奎醚等量)20 min后加内毒索.所有组加药后放置培养箱,4 h后加肿瘤坏死因子α(TNF-α)、白细胞介素-6(IL-6)、白细胞介素-10(IL-10)检测试剂.结果 与Ⅰ组相比,Ⅱ、Ⅲ、Ⅳ、Ⅴ组TNF-α、IL-6、IL-lO水平均明显增高;与Ⅱ组相比,Ⅲ、Ⅳ组TNF-α、IL-6、IL-10水平均有不同程度的下降(P<0.01),且Ⅲ组下降程度较Ⅳ组更明显(P<0.05),Ⅴ组TNF-α、IL-6、IL-10水平虽有所变化,但差异无统计学意义.结论 抗胆碱药能作用于白细胞非神经性胆碱能受体,抑制白细胞炎性介质的分泌,盐酸戊乙奎醚的作用更明显,尤以提前干预为佳.     

安定-氯胺酮麻醉对烧伤小鼠早期炎症反应的影响

目的研究安定-氯胺酮麻醉对烧伤小鼠腹腔巨噬细胞糖皮质激素受体(GR)及血清炎性细胞因子的影响,探讨其对创伤早期炎症反应的作用.方法 120只BALB/C健康雄性小鼠随机分为正常对照组、烧伤对照组、麻醉对照组、先处理组(麻醉后15 min烧伤)、后处理组(烧伤后15 min麻醉).采用安定-氯胺酮麻醉,小鼠烧伤模型为背部15%～20%Ⅲ度烧伤.于烧伤或麻醉后4 h颈椎脱臼法处死小鼠,收集全血及腹腔巨噬细胞.采用ELISA法测定血清肿瘤坏死因子(TNF-α)、IL-1β、IL-10浓度,采用Western blot技术测定腹腔巨噬细胞GR表达.取部分正常对照组和烧伤对照组腹腔巨噬细胞在体外与安定、氯胺酮共同培养,并测定腹腔巨噬细胞GR水平.结果与正常对照组比较,烧伤对照组血清TNF-α、IL-1β、IL-10浓度增高,先处理组血清IL-10浓度增高,后处理组血清IL-10浓度增高(P＜0.01);与烧伤对照组比较,先处理组和后处理组血清TNF-α、IL-1β、IL-10浓度降低(P＜0.01或0.05).与正常对照组比较,烧伤对照组、麻醉对照组和后处理组腹腔巨噬细胞GR表达水平降低(P＜0.05或0.01);与烧伤对照组比较,先处理组和后处理组腹腔巨噬细胞GR表达水平明显增高(P＜0.05或0.01);与先处理组比较,后处理组GR表达水平明显降低(P＜0.05).正常组或烧伤组腹腔巨细胞经安定-氯胺酮培养后GR表达差异无统计学意义(P＞0.05),正常组GR表达高于烧伤组(P＜0.01).结论安定-氯胺酮麻醉对小鼠烧伤后腹腔巨噬细胞GR表达水平下调以及炎性细胞因子的释放有一定抑制作用.     

骨髓间充质干细胞对小鼠缺血-再灌注急性肾损伤中IL-10和TNF-α表达的影响

目的探讨骨髓间充质干细胞(BMSC)对小鼠缺血-再灌注急性肾损伤(IR-AKI)过程中白细胞介素(IL)-10和肿瘤坏死因子(TNF)-α表达的影响。方法将小鼠随机分为假手术组(对照组)、缺血-再灌注损伤组(IRI组)和BMSC治疗组(BMSC组),每组6只。检测各组小鼠肾功能及病理学改变;检测各组小鼠肾组织细胞凋亡情况;检测各组小鼠血清IL-10和TNF-α的表达水平。将小鼠BMSC随机分为对照组和缺氧复氧组(IRI组),检测各组细胞上清IL-10和TNF-α的表达水平。结果对照组小鼠肾组织结构正常,IRI组肾组织结构损伤严重,BMSC组损伤较轻。与对照组比较,IRI组和BMSC组肾组织损伤评分较高;与IRI组比较,BMSC组小鼠肾组织损伤学评分较低(均为P0.05)。与对照组比较,IRI组小鼠血清肌酐(Scr)和血尿素氮(BUN)水平升高,BMSC组BUN水平升高;与IRI组比较,BMSC组小鼠Scr和BUN水平下降(均为P0.05)。IRI组肾组织凋亡细胞数量多于BMSC组和对照组,BMSC组凋亡细胞数量多于对照组(均为P0.05)。与对照组比较,IRI组小鼠血清IL-10和TNF-α水平均升高,BMSC组小鼠血清TNF-α水平下降,IL-10水平升高;与IRI组比较,BMSC组小鼠血清IL-10和TNF-α水平均下降(均为P0.05)。IRI组细胞上清IL-10、TNF-α水平与对照组比较,差异均无统计学意义(P=0.080、0.627)。结论 BMSC输注可降低肾IRI及炎症反应,其机制可能是通过抑制TNF-α表达,而非促进IL-10的表达。     

银杏达莫注射液对早期糖尿病肾病患者TNF-α和IL-6的影响

目的:探讨银杏达莫注射液对早期糖尿病肾病(DN)患者血清肿瘤坏死因子-α(TNF-α)和白细胞介素-6(IL-6)的影响.方法:将76例早期DN患者随机分为对照组和治疗组,每组38例,对照组给予常规治疗,治疗组在常规治疗基础上加用银杏达莫注射液,治疗2周,治疗前后检测两组患者FBG、UAER、TNF-α和IL-6指标.结果:治疗前,两组患者FBG、UAER、TNF-α和IL-6水平比较,差异无统计学意义(P＞0.05);治疗后,治疗组患者FBG、UAER、TNF-α和IL-6水平均明显低于对照组(P＜0.01).结论:银杏达美注射液能够降低早期DN患者血清TNF-α和IL-6水平,抑制炎症反应.     

吸入NO对婴幼儿体外循环中细胞因子变化的影响及意义

目的 探讨吸入一氧化氮(NO)对婴幼儿体外循环手术中细胞因子变化的影响及意义.方法 室间隔缺损的婴幼儿30例随机分为对照组和NO组,NO组在体外循环期间吸人40×10-6NO直至关胸.在体外循环前、主动脉开放后1、3、5、10 min分别取右上肺静脉血和右心房血测定TNF-α、IL-8、IL-10.结果 NO组IL-10水平较对照组增高(P<0.01),TNF-α、IL-8则较对照组明显降低(P<0.05).结论 NO能抑制炎症性细胞因子,促进抗炎细胞因子的活性,故可减轻体外循环并发症.     

高氧液对严重烧伤休克期羊淋巴循环TNF-α、IL-6、IL-8水平的影响

目的：研究高氧液对严重烫伤休克期羊淋巴循环TNF-α、IL-6、IL-8水平的影响。方法：将20只成年雌性羊随机分为2组,A高氧液组（10只）和B对照组（10只）,2组均造成30%TBSAⅢ度烧伤,分别输入高氧液和平衡盐液,经股前淋巴管插管收集淋巴液,用放射免疫分析法检测伤后6、24、48h淋巴液TNF-α、IL-6、IL-8水平的变化,同时测定血氧饱和度（SaO2）。结果：烧伤休克期A组各时相点淋巴液TNF-α、IL-6、IL-8水平显著低于B组。A组SaO2明显高于B组。结论：高氧液对严重烧伤休克期羊淋巴循环有改善作用,降低淋巴液中TNF-α、IL-6、IL-8的水平。     

利奈唑胺对严重烧伤家兔炎症因子水平的影响

目的：研究利奈唑胺（LZD）对严重烧伤家兔促炎症因子肿瘤坏死因子-α（TNFα）、白介素-1β（IL-1β）、白介素-6（IL-6）水平的影响。方法：随机将24只家兔分为假烫组、烫伤组、假烫＋LZD治疗组、烫伤＋LZD治疗组4组,每组6只。将两烫伤组家兔背部皮肤置于98℃热水18s制备30％TBSAI III度烫伤模型;假烫组用37℃温水代替热水。两LZD治疗组家兔静脉注射10mg／kg利奈唑胺。组织病理学观察烫伤深度,采用放射免疫分析方法检测烧伤后家兔血清TNF—α、IL-1、β、IL-6水平。结果：与假烫组家兔比较,烧伤家兔TNF-α、IL-1β及IL-6显著升高,IL-1β在伤后12h达峰值,TNF-α及IL-6在伤后24h达峰值。利奈唑胺能显著降低烫伤家兔TNF-α、IL-1β及IL-6水平（P〈0．05）,降幅分别为28．19％、38．54％和28．48％,但利奈唑胺对假烫家兔3种细胞因子的水平无显著影响（P〉0．05）。结论：利奈唑胺能显著降低烫伤家兔的促炎症因子水平。     

不同免疫调节方式对烧伤脓毒症大鼠炎性反应的影响

Objective To investigate the effect of Thymosin and growth hormone(GH) on inflam-matory response in burn rats or burn rats with sepsis. Methods Sixty-four SD rats were randomly divided into normal control group (NC, without treatment), sepsis group (S, with injection of LPS), sepsis + Thy-mosin group (ST, with successive injection of Thymosin and LPS), sepsis + GH group [SGH, with succes-sive injection of recombinant human GH (rhGH) and LPS], burn group, burn + sepsis group (BS, with in-jection of LPS after burn), burn + sepsis + Thymosin group (BST, with successive injection of Thymosin and LPS after burn), burn + sepsis + GH (BSGH, with successive injection of rhGH and LPS after burn), with 8 rats in each group. Specimens of spleen tissues were harvested to determine HLA-DR in lymphocyte and e-valuate inflammatory cell infiltration (score). Specimens of peripheral blood were collected to determine Toll-like receptor 4 (TLR4) level in monocyte and serum level of TNF-α, IL-4, IL-6, IL-10. Results Compared with those in NC group, serum level of IL-10 in S group decreased obviously, while other indices increased obviously (P<0.01). The levels of HLA-DR and TLR4 and serum level of TNF-α were similar between SGH and ST groups (P>0.05). Compared with those in SGH group [(2.87±0.04) score, and IL-6 (0.0083±0.0018) μg/mg, IL-4 (0.0102±0.0021) μg/mg, IL-10 (0.0310±0.0027) μg/mg, re-spectively], degree of inflammatory cell infiltration (1.50±0.76) score and serum levels of IL-6, IL-4, IL-10 of rats in ST group decreased obviously (0.0064±0.0012, 0.0058±0.0024, 0.0230±0.0021 μg/mg, respectively, P<0.01). The levels of HLA-DR, TLR4 and inflammatory cell infiltration degree of spleen in B group were respectively higher than those in NC group and lower than those in BS group. Com-pared with those in NC group, serum levels of TNF-α, IL-6 in B group increased significantly, while IL-4, IL-10 showed an opposite tendency. There was no obvious difference between BST and BSGH groups in ser-um levels of HLA-DR and IL-6 (P>0.05). Compared with those in BST group, inflammatory cell infiltra-tion degree in spleen and the levels of TLR, TNF-α obviously decreased (P<0.01), while IL-4 and IL-10 levels increased in BSGH group (P<0.01). Conclusions Inhibitive effects between Thymosin and GH on extensive inflammatory reaction were similar with or without trauma, and GH has better effect as compared with Thymosin when with trauma.     

大鼠自体原位肝移植术后早期小肠黏膜损伤的病理及炎症因子变化特点

目的观察大鼠自体原位肝移植术后早期不同时期小肠黏膜病理变化特点与肿瘤坏死因子（TNF）-α、白介素（IL）-1β和IL-6水平的动态变化,探讨肝移植术后肠道损伤的发生机制。方法Sprague—Dawley（SD）大鼠25只,随机分为假手术组（S组）和模型组（R组）：假手术组大鼠开腹后只进行肝血管的分离,模型组大鼠建立自体原位肝移植模型,在肝脏阻断20min后,根据再灌注时间不同分为再灌注后4、8、16、24h4个亚组（即R4组、R8组、R16组和R24组）,每组各5只动物。检测各组小肠黏膜组织病理学改变与小肠组织IL-1β、TNF—α和IL-6水平变化。结果在光镜下观察发现S组大多数未见明显病理改变,各模型组肠组织光镜下可见上皮层结构出现破坏,由最初的绒毛尖端上皮下间隙增大逐渐发展到上皮层与固有层大量分离,累及绒毛两侧,部分绒毛顶端甚至出现破损,这些病理改变在R8和R16组达到高峰,然后逐渐恢复。与S组比较,各模型组Chiu’s评分增高（均为P〈0．05）;各模型组相比,R8组、R16组较R4组、R24组Chiu’s评分增高（均为P〈0．05）。与S组比较,R16组肠组织TNF-α、IL-1β和IL-6水平均增高（P〈0．05）;各模型组的肠组织TNF-α、IL-1β、IL-6在肝脏再灌注后4h（R4组）开始升高,在16h达到高峰（R16组）,在24h开始逐渐恢复（R24组）。结论大鼠自体原位肝移植术后早期出现小肠黏膜损伤,4h内损伤逐渐加重,24h开始逐渐恢复;该损伤可能与小肠组织炎症因子TNF—α、IL-1β和IL-β6的改变相关。     

血必净联合维拉帕米对大鼠小肠缺血再灌注损伤的实验研究

目的探讨血必净联合维拉帕米对大鼠小肠缺血再灌注（I／R）损伤的保护作用及其可能机制。方法制作小肠缺血再灌注模型,SD大鼠50只随机分为假手术组（A组）、缺血再灌注组（B组）、血必净组（c组）、维拉帕米组（D组）及血必净和维拉帕米联合治疗组（E组）,各10只。分别检测各组大鼠小肠缺血45min再灌注0h、2h时血清中肿瘤坏死因子α（TNF—α）、白细胞介素1β（IL-1β）、丙二醛（MDA）的含量;同时观察小肠黏膜组织病理学变化。结果缺血再灌注组小肠组织病理学改变较其他组明显;在再灌注0h、2h时B、C、D、E组血清中TNF—α、IL-1β、MDA含量均较A组显著升高（P〈0．05）;再灌注2h时C、D、E组血清中TNF—α、IL-1β、MDA含量均较B组明显降低（P〈0．05）,但C、D两组间差异无统计学意义;C、D组血清中TNF—α、IL-1β、MDA含量均较E组明显升高（P〈0．05）。结论血必净、维拉帕米能减轻大鼠小肠缺血再灌注损伤,二者联合用药有协同保护作用,效果更明昴。     

Clostridial collagenase aggravates the systemic inflammatory response in rats with partial-thickness burns

AimClostridial collagenase A (CCA) has been shown effective in degrading collagen in eschar tissue and promoting healing in partial-thickness burns. As there are also reports of fever, leukocytosis, increased C-reactive protein (CRP) levels and septic complications during treatment with CCA, we aimed to determine in rats whether CCA aggravates the systemic inflammatory response.MethodsRats with partial-thickness burns were randomly divided into groups with either no dressing (ND), povidone-iodine dressing (PID) or CCA dressing (CCAD). Body weights and temperatures, blood leukocyte counts, and serum levels of CRP, interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumour necrosis factor-α (TNF-α), were measured at 0, 3, and 24 h and days 3 and 7 from burn. Wounds were cultured on days 1, 3 and 7 and burn depth was evaluated on day 1.ResultsBody weights for all groups were significantly lower after burn, with highest loss (25.5%) in the CCAD group. At 3 h a significant drop in rectal temperature was noted in all groups. The CCAD group had higher rectal temperature levels than the PID group on days 3 and 7 (p < 0.05). Changes in serum levels of CRP, IL-1β, IL-6 and TNF-α were not significant in the ND and PID groups; the CCAD group showed a significant rise in serum levels of CRP on day 1, of IL-6 on day 3 and of TNF-α on day 7. Wound infection was more common in CCAD group and increased on days 3 and 7, but this was insignificant.ConclusionCCA aggravated the systemic inflammatory response in rats with partial-thickness burns, which is accompanied by a higher risk of infection.     

乌司他丁对脂多糖所致内毒素血症大鼠胃肠黏膜循环的影响

目的：探讨乌司他丁（ulinastatin, UTI）对脂多糖所致内毒素血症大鼠胃肠黏膜循环的影响。方法30只雄性Wistar 大鼠随机分成3组,正常对照组（ NC组）、脂多糖（ Lipopolysaccharide , LPS）处理组（ LPS组）和乌司他丁处理组（ UTI组）,每组10只。正常对照组只麻醉不处理,脂多糖组和乌司他丁组经腹腔注射脂多糖5 mg/kg,乌司他丁组于脂多糖注射前经尾静脉静注乌司他丁50000 U/kg。分别于处理前、脂多糖注射后3、6和12 h检测胃黏膜pH（ pHi）值,同时经股静脉抽血检测肿瘤坏死因子-α（ TNF-α）、白细胞介素-6（ IL-6）。采用SPSS 13．0软件进行统计学分析,结果以均数±标准差（ x珋±s）表示。各时间点组间比较采用单因素方差分析,P＜0．05为差异有统计学意义。结果经脂多糖处理后,大鼠3 h后血浆TNF-α和IL-6含量即开始逐渐升高,胃黏膜pH逐渐降低;与脂多糖组比,乌司他丁组在T3、T6和T12时间点TNF-α含量明显降低（ T3： P＝0．044; T6： P＝0．035;T12：P＝0．033）, IL-6含量明显降低（T3：P＝0．041; T6： P＝0．022; T12： P＝0．024）,胃黏膜pH明显升高（T3：P＝0．003;T6：P＝0．028;T12：P＝0．012）。结论乌司他丁可降低内毒素血症大鼠外周血TNF-α和IL-6浓度,增加胃黏膜pH值,改善胃肠黏膜灌注。     

抑制低氧诱导因子-1α表达对小鼠肠缺血／再灌注所致肺损伤的影响

目的探讨通过低氧诱导因子-1α（hypoxiainduciblefactor-1α,HIF—1α）抑制剂YC-1预先抑制该基因表达对肠缺血,再灌注（ischemia／reperfusion,I／R）致急性肺损伤的影响。方法6周～8周龄健康雄性C57BL／6小鼠36只,采用随机数字表法随机分为3组（每组12只）：假手术组（S组）、I／R组和I／R±YC—I预处理组（YC—I组）。YC-1组于术前10min腹腔注入YC-1（1mg／kg）,采用夹闭C57BL／6小鼠肠系膜前动脉45min后再灌注6h的方法造成肠YR损伤模型,取小鼠肺标本称重后计算肺湿干重比,苏木素-伊红（hematoxylin-eosin,HE）染色后观察肺组织病理学改变,分光光度法测定髓过氧化物酶（myeloperoxidase,MPO）活性、酶联免疫吸附测定法检测肺组织肿瘤坏死因子-α（tumor necrosis factor-α,TNF-α）和白细胞介素（interleukin,IL）-1β表达,反转录-PCR法检测HIF-1α、Toll样受体4（toll—likereceptor4,TLR4）mRNA的表达。结果与I／R组比较,预先抑制HIFqct表达使肺实质水肿及中性粒细胞浸润聚集减少,肺组织病理学损伤减轻,肺湿干重比显著降低（RnOI）,MPO活性下调[（1．88±0．82）u／g],TNF-α[（187±20）ng／L）]、IL一1β[（536±54）ng／L）]、HIF-1α、TLR4mRNA的表达水平下降（P〈0．05）。结论YC-1预处理可使肺组织TLR4mRNA表达下调,抑制肠I／R肺组织中促炎细胞因子的释放,明显减轻小鼠肠I／R后急性肺损伤。     

Role of intestinal bifidobacteria in the pathogenesis of gut-derived bacteria/endotoxin translocation and the effect of bifidobacterial supplement on gut barrier function following burns

Early multiple organ dysfunction syndrome appears to be facilitated with bacterial translocation in severely burn injury, yet the mechanisms of bacterial translocation remains in dispute. The aim of this study was to investigate the potential role of intestinal bifidobacteria in the pathogenesis of gut-derived bacteria/endotoxin translocation following burns and the effects of bifidobacterial supplement on gut barrier. Methods: Wistar rats were randomly divided into burn group (Burn, n=60),sham burn group (SB, n=10) in experiment Ⅰ , and burn + saline group (BS, n=30), burn + bifidobacteria group (BB, n=30), and sham-burn + saline group (SS, n= 10) in experiment Ⅱ. Animals in BB group were fed bifidobacterial preparation (5 × 109 CFU/ml) after burns, 1.5ml,twice daily. Animals in BS and SS were fed saline. Samples were taken on days 1, 3, and 5 in burn groups, and on day 3 in sham-burn groups. The incidence of bacteria/endotoxin translocation and counts of Bifidobacterium, Fungi and Escherichia coli in gut mucosa were determined with standard methods. The levels of sIgA in mucus of small intestine were measured by RIA. The positive sIgA expression in lamina propria and ileum mucosal injury was evaluated light microscopically by blinded examiners. Results: Our results showed that the incidence of bacterial translocation was increased after burns, which was accompanied by significant decrease in number of bifidobacteria but significant increase in E. coli and fungi in gut mucosa, and elevation of levels of plasma endotoxin and IL-6 (P<0. 001).The incidence of bacterial translocation was markedly reduced after 3- and 5-day supplementation of bifidobacteria compared with control group (P<0.05). The counts of mucosal bifidobacteria were increased by 4- to 40-fold,while E. coli and fungi were decreased by 2- to 30-fold and 10- to 150-fold, respectively, after bifidobacterial supplementation in contrast to control group. The damage of mucosa tended to be less pronounced after 3-day bifidobacteria-supplemented formula compared with control group [grade 2(0-6) vs. grade 4(3-6), P<0.05]. Moreover, the expression and release of sIgA was markedly augmented after 3-day bifidobacteria-supplementation formula and it returned to normal range on day 5. Conclusion: The decrease in counts and proportion of bifidobacteria in mucous membrane flora may play an important role in the development of bacteria/endotoxin translocation following thermal injury. The supplement of exogenous bifidobacteria could per se improve gut barriers, and attenuate bacteria/endotoxin translocation secondary to major burns.     

Effects of early excision and grafting on cytokines and insulin resistance in burned rats

Burn wound excision and grafting is a common clinical practice that decreases patient morbidity and mortality. It is not known, however, if the salutary effects of this procedure are related to effects on interleukin 6 (IL-6) and tumor necrosis factor (TNF-) α, and to reducing insulin resistance after burn. Sprague–Dawley rats were randomly divided into three groups: control, burn, burn ± excision groups. Rats in burn group were given a third-degree scald burn covering 30% total body surface area (TBSA) and no wound excision. Rats in burn ± excision group were subjected to a 30% third-degree burn followed by complete excision and allografting of the injury site within 15 min after burn. The rats in control group were treated in the same manner as the burn group, except that they were immersed in a room-temperature water. Glucose tolerance tests (GTT) were observed at 3 days after burn, euglycemic–hyperinsulinemic glucose clamps were performed at 4 days after burn and interleukin 6 (IL-6) and tumor necrosis factor (TNF-) α were determined after euglycemic–hyperinsulinemic glucose clamps. The levels of IL-6 and TNF-α increased after burn. Significant differences in GTT were observed between control and burn groups, and the rate of glucose infused measured in burned rats was significantly decreased compared with that in control at 4 days after burn. Early excision and grafting significantly decreased levels of IL-6 and TNF-α, and further reduced insulin resistance following thermal injury compared with burn group. Conclusion: Early excision and grafting appeared to have an effect on inflammatory mediators and further reduced insulin resistance induced by major burns.