人参二醇组皂苷对内毒素休克大鼠体内血管活性物质的调节作用

目的 探讨人参二醇组皂苷(PDS)对内毒素休克大鼠体内血管活性物质的调节作用.方法 大鼠舌下静脉注射PDS进行预治疗,10 min后注射细菌内毒素(LPS,5 mg/kg)复制感染性休克模型.实验动物随机分为对照组(C组),内毒素休克组(L组),地塞米松预治疗组(LD组),PDS预治疗组(LP组).各组大鼠于休克2、4 h腹主动脉取血,硝酸还原酶法测定血清中一氧化氮合酶(NOS) 活性和NO-2/NO-3的变化,间接反映NO的水平.于休克后4 h处死动物,称取肝组织20 mg匀浆后测血栓素B2(TXB2)及6-酮-前列腺素F1α(6-Keto-PGF1α)的含量.结果 肝组织中TXB2、6-keto-PGF1α及6-Keto-PGF1α/TXB2在LP组均显著低于L组.注射内毒素2 h后L组的血清NOS和NO-2/NO-3明显升高,LD组和LP组NOS活性、NO-2/NO-3显著低于L组.结论 PDS能够降低内毒素休克大鼠TXA2、PGI2和NO的水平,改善微循环状态,起到抗休克的作用.     

人参二醇皂苷对感染性休克大鼠血清心肌酶和心肌超微结构的影响

目的观察人参二醇皂苷(PDS)对感染性休克大鼠心肌酶和心肌细胞超微结构的影响。方法大鼠舌下静脉注射PDS进行预治疗,10min后注射细菌内毒素(LPS,5mg/kg)复制感染性休克模型。实验动物随机分为对照组;LPS组;地塞米松(LPS+Dex)组;人参二醇皂苷(LPS+PDS)组。颈动脉插管记录平均动脉压(MAP);分别于休克后2h和4h腹主动脉取血,测定天门冬氨酸氨基转移酶(AST)、肌酸激酶(CK)、乳酸脱氢酶(LDH)含量及电镜观察心肌细胞超微结构的改变。结果注射LPS后,LPS组的MAP迅速下降,在低水平维持,LPS+Dex组和LPS+PDS组的MAP未见明显下降,优于模型组(P0.01);注射LPS4h后LPS组的AST、CK、LDH均明显升高,LPS+Dex组和LPS+PDS组心肌酶含量显著低于LPS组(P0.01)。结论 PDS能够明显改善LPS休克大鼠的低血压状态,降低心肌酶活性,减轻心肌细胞超微结构的损伤程度。     

人参二醇皂苷对急性血瘀大鼠肠系膜微循环和血栓形成的影响

目的探讨人参二醇皂苷（Panaxdiols Saponin,PDS）活血化瘀的药理作用。方法皮下注射肾上腺素加冰水冷浴法制备大鼠急性血瘀模型,舌下静脉注射给药,观察PDS对大鼠肠系膜微循环及体外血栓各指标的影响。结果PDS10,20 mg/kg剂量组均能明显加快微动脉、微静脉血流速度,增加微血管管径、血管数、和血管开放数,改善血液流态,并能抑制体外血栓的形成（P〈0.05;P〈0.01）。结论PDS能明显改善血瘀型大鼠肠系膜微循环障碍,抑制血栓的生成,具有较好的活血化瘀作用。     

血栓心脉宁片对大鼠肠系膜微循环障碍的改善作用

目的 研究血栓心脉宁片对大鼠肠系膜微循环障碍的影响.方法 将Wistar大鼠随机分为模型组(灌胃予蒸馏水)、血栓心脉宁片低剂量组(予血栓心脉宁350 mg/kg体重)、中剂量组(予血栓心脉宁700 mg/kg体重)、高剂量组(予血栓心脉宁1400 mg/kg体重),步长脑心通阳性对照组(予步长脑心通800 mg/kg体重).各组大鼠每日灌胃给药1次,第5日给药30 min后,舌下静脉给药10％高分子右旋糖酐造成大鼠肠系膜微循环障碍模型.微循环显微分析系统记录各组肠系膜微动脉血流流速、血管管径的变化差值和红细胞流态.结果 血栓心脉宁片中、高剂量组均能使10％高分子右旋糖酐引起的大鼠肠系膜毛细血管收缩时间缩短,促进微循环障碍恢复.结论 血栓心脉宁片中、高剂量对大鼠微循环障碍有改善作用.     

人参二醇皂甙对内毒素休克大鼠肾组织CD14和IL-18表达的影响

目的 探讨人参二醇皂甙对内毒素休克大鼠肾组织损伤保护作用的分子机制.方法 选用成龄Wistar大鼠为研究对象,随机分为空白对照组(CTR)、LP模型组(LPS)、人参二醇皂苷预防治疗组(PDS).以LPS 5 mg/kg舌下静脉注射复制内毒素休克模型,以平均动脉血压下降至基础血压的2/3判定为休克状态.LPS注射前10 min,PDS组腹腔注射人参二醇皂苷(20 mg/kg),于休克240 min时处死动物,提取肾组织,利用免疫组化方法观察人参二醇皂甙对内毒素休克大鼠肾脏病理组织学变化的影响,利用Westerm印迹检测各组大鼠肾脏中CD14和IL-18的蛋白表达差异.结果 免疫组化结果显示,PDS组肾脏CD14的阳性表达程度低于LPS组,CD14强表达的组织细胞少于LPS组.Westerm印迹结果显示,与对照组相比,模型对照组大鼠肾脏组织CD14、IL-18蛋白表达水平明显升高,而PDS组能显著降低两种蛋白的表达水平(P＜0.05).结论 PDS对内毒素休克大鼠肾损伤有保护作用,可能通过抑制LPS介导的CD14信号转导通路的过度激活,减少IL-18等炎症介质的分泌,实现对肾脏的保护作用.     

人参皂苷Rg2对内毒素性微循环障碍的影响

目的　观察人参皂苷Rg2 对内毒素性微循环障碍的影响。方法　用大肠杆菌内毒素建立微循环障碍模型 ,分别观察动物肠系膜或耳部微动脉管径和血流状态。结果　人参皂苷Rg2 5、1 0mg/kg ,iv,山莨菪碱 2 5mg/kg均明显增加大鼠肠系微循环血流速度 ,抑制微动脉收缩 ,人参皂苷作用强度略高于山莨菪碱 ;人参皂苷Rg2 0 .85、1 .7mg/kg能使家兔耳廓微动脉明显扩张 ,血流速度也有所增加。 结论　人参皂苷Rg2 有明显的改善微循环障碍作用     

人参二醇皂甙对内毒素休克大鼠肾组织的保护作用

目的探讨人参二醇皂甙对内毒素休克大鼠肾组织损伤的保护作用。方法将成龄Wistar大鼠随机分为对照组(CTR),LPS模型组(LPS)及人参二醇皂甙预防治疗组(PDS)。以LPS 5 mg/kg舌下静脉注射复制内毒素休克模型,以平均动脉血压下降至基础血压的2/3判定为休克状态,利用股动脉插管记录平均动脉压(MABP)。在动物休克4 h时将其处死,提取肾组织,显微镜下观察肾脏病理组织学变化。取动物腹腔静脉血,分离血清,检测一氧化氮合酶(NOS)、一氧化氮(NO)、超氧化物歧化酶(SOD)和丙二醛(MDA)的含量。结果 LPS组肾小球扩张充血,肾小管上皮细胞明显肿胀与空泡变性,胞质深染,偶见坏死病灶,间质中炎细胞浸润。PDS组肾脏组织学变化明显轻于LPS模型组。动物休克4 h时,LPS组血清NOS和NO含量显著高于CTR组(P<0.01),PDS组血清NOS和NO含量显著低于LPS模型组(P<0.05);LPS组血清MDA含量显著高于CTR组(P<0.01),PDS组血清MDA含量显著低于LPS组(P<0.05)。结论人参二醇皂甙能显著提高内毒素休克大鼠的抗脂质过氧化能力,对肾脏组织有保护作用。     

硫代乙酰胺致大鼠肠源性内毒素血症模型探讨

目的 探讨不同剂量硫代乙酰胺(TAA)所制备的大鼠肠源性内毒素血症(IETM)模型的量效关系.方法 将40只大鼠分为4组,每组10只.TAA组分别以200、400、600mg/kg剂量的TAA灌胃,24h后相同剂量TAA重复灌胃一次,建立不同剂量TAA致大鼠IETM的动物模型;健康对照组以等体积0.9%氯化钠溶液灌胃.观察造模后24、48h大鼠死亡情况,48h后采集存活大鼠腹主动脉血,检测血浆内毒素、血清ALT和AST,观察肝组织病理变化.采用单因素方差分析,组间比较采用t检验.结果 造模48h后,健康对照组无大鼠死亡,200mg/kgTAA模型组死亡2只,400mg/kg TAA模型组死亡5只,600mg/kg TAA模型组死亡8只.200、400、600mg/kg TAA模型组大鼠血清ALT水平分别为(305.09±116.78)、(901.67±274.31)和(1454.84±473.49)U/L,明显高于健康对照组的(47.81±22.61)U/L(t=14.583、25.896、20.596,均P＜0.05);200、400、600mg/kg TAA模型组大鼠血清AST水平分别为(465.88±139.96)、(884.37±250.90)和(1889.23±159.67)U/L,明显高于健康对照组的(69.33±22.04)U/L(t=12.988、18.455、13.542,均P＜0.05);200、400、600mg/kg TAA模型组大鼠血浆内毒素水平分别为(0.436±0.110)、(0.550±0.095)和(0.620±0.057)EU/mL,明显高于健康对照组的(0.103±0.056)EU/mL(t=7.335、5.260、8.191,均P＜0.05).病理学显示不同剂量TAA模型组有不同程度的肝细胞变性坏死.结论 TAA剂量为200～600mg/kg时可成功制作IETM模型,200mg/kg TAA模型组大鼠死亡率较低,适于进一步的实验研究.     

小蔓长春花提取物对脑缺血大鼠血液流变学及抗氧化能力的影响

目的 观察小蔓长春花提取物(VMLE)对脑缺血大鼠血液流变学及抗氧化能力的影响.方法 选择SD大鼠80只,采用Zea-Longa腔内线栓法制作大鼠大脑中动脉缺血模型,成模大鼠共50只.随机将大鼠分为模型组、尼莫地平组[ 10 g/(kg·d)]、VMLE高剂量组[10g/(kg·d)]、VMLE低剂量组[5 g/(kg·d)]和假手术组各10只,分别给予相应药物灌胃2d,48 h后测定大鼠血液流变学和抗氧化能力.结果 VMLE高、低剂量组均能明显降低脑缺血大鼠全血黏度、血浆黏度、红细胞压积、红细胞聚集指数、红细胞刚性指数,并能增强超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-PX)活性,降低丙二醛(MDA)含量(P均＜0.05);尼莫地平组能增强SOD、GSH-PX活性,降低MDA含量,但对脑缺血大鼠全血黏度、血浆黏度、红细胞压积无明显影响.结论 预防性应用VMLE可改善脑缺血大鼠血液流变学及抗氧化能力.     

人参二醇组皂苷对失血性休克犬心肌收缩功能和血氧饱和度的影响

目的观察人参二醇组皂苷(Panaxdiols Saponin,PDS)对失血性休克犬心肌收缩功能、血氧分压(PaO2)、血氧饱和度(SaO2)及红细胞压积(HCT)的影响。方法制备犬失血性休克病理模型,动脉放血至平均动脉压(MAP)在5.33kPa以下,然后静脉滴注PDS12.5,25mg/kg,地塞米松磷酸钠注射液(DXMT)1mg/kg。测定犬心肌收缩功能、动脉血气和HCT的变化。结果 PDS使失血性休克犬MAP、左室收缩压(LVSP)及左室内压最大变化速率(±dp/dtmax)显著升高;血气PaO2和SaO2明显上升;HCT下降。结论 PDS可明显改善失血性休克犬血流动力学状态,提高血氧含量,减轻组织缺血缺氧及微循环障碍,对失血性休克犬具有保护作用。     

Metronidazole improves intestinal microcirculation in septic rats independently of bacterial burden

To explore the effects of metronidazole (Me) on intestinal microcirculation in septic rats, intravital microscopy (IVM) following 16 hours of colon ascendens stent peritonitis (CASP model) was used. Four groups of animals were studied: control group (sham operation) and CASP group, each with and without Me treatment (10 mg/kg i.v.). In order to investigate the substance-specific effects of Me independently of the antibacterial effects within a pathologically altered microcirculation, a second experimental series with lipopolysaccharide challenge (LPS model) was carried out. The LPS model consisted of the four groups (control animals and LPS animals (15 mg/kg i.v. LPS from E. coli) with and without Me). IVM in the LPS experiments was performed following a two hour observation period. Me treated CASP or LPS animals, as compared with untreated, demonstrated significant improvement of functional capillary density (FCD) of the intestinal wall. The increase in the number of leukocytes firmly adhered to the endothelium (leukocyte sticking) in the untreated CASP or LPS animals within the V1 venules of the intestinal submucosal layer, was significantly reduced in the Me treated animals. In conclusion, Me exerts beneficial anti-bacterial and anti-inflammatory effects within the septic microcirculation.     

Hemodynamic and hepatic microcirculational changes in endotoxemic rats treated with different NOS inhibitors

BACKGROUND/AIMS: Severe septic shock may produce hypotension, which is due to the vasodilatational effect of nitric oxide. The effects of different nitric oxide synthase inhibitors on the hemodynamic and hepatic microcirculation of the endotoxemic rats were studied. METHODOLOGY: A prospective controlled study was performed. Eighteen Sprague-Dawley male rats (250-300 g) were anesthetized and studied. The rats were divided into three groups. The rats in group A (n = 6) were injected with lipopolysaccharide (50 mg/kg BW) and L-NAME (5 mg/kg BW). The rats in group B (n = 6) were injected with the same dose of lipopolysaccharide and aminoguanidine (400 mumole/kg BW). The rats in group C rats (n = 6) were injected with same dose of lipopolysaccharide and normal saline as a control. The rats were cannulated with femoral arterial, venous, and jugular venous catheters. Cardiac output was measured using a thermodilutional method, and liver sinusoidal microcirculation was measured with Laser Doppler Flowmetry. The cardiac output, stroke volume, heart rate, blood pressure, and microcirculational flux of the liver in the three groups were measured and compared at 0, 20, 40, 60 and 80 minutes after injection. RESULTS: The rats of group A showed significant decrease of their cardiac output, stroke volume and hepatic microcirculation after the drugs were infused though their blood pressure increased. The rats of group B showed decrease of their blood pressure and stroke volume initially, but no significant change of their cardiac output and hepatic microcirculation. At the 80th min, the rats of group B had the significantly highest cardiac output, stroke volume and hepatic microcirculation among three groups. CONCLUSIONS: The aminoguanidine prevents the hypotensive effect as well as L-NAME during severe sepsis, but it can maintain cardiac output, stroke volume and hepatic microcirculation better than L-NAME.     

乌司他丁对内毒素血症大鼠心肌TOLL样受体4表达的影响

目的 观察乌司他丁对脂多糖(Lipopolysaccharides,LPS)诱导心肌TOLL样受体4(TLR4)受体表达的影响及与炎症反应的关系.方法 选取8周龄的雄性SD大鼠32只,分成四组:正常对照组,内毒素血症组(LPS组),LPS+乌司他丁组,LPS+地塞米松组.除正常对照组以外,其余三组给予脂多糖8 mg/kg大鼠阴茎静脉注射,LPS+乌司他丁组与LPS+地塞米松组分别同时给予乌司他丁2.5万/kg、地塞米松5 mg/kg;正常对照组给予同量的生理盐水,3h后断头取血并取心肌液氮保存;ELISA法测血浆TNF-α的水平;放免法测定心肌组织中AngⅡ水平;RT-PCR法测定心肌组织TLR4 mRNA表达;免疫组化法和蛋白免疫印迹法测心肌组织TLR4含量.结果 (1)LPS组TNF-α、CRP、IL-6水平和心肌AngⅡ水平显著增高;与LPS组相比,乌司他丁组TNF-α 、CRP、IL-6和心肌AngⅡ显著降低(2)LPS可明显增加心肌中TLR 4 mRNA及蛋白表达,乌司他丁明显抑制心肌TLR4 mRNA及蛋白的表达.结论 乌司他丁能抑制LPS诱导大鼠心肌的炎症反应.乌司他丁能降低LPS诱导大鼠的心肌TLR4 mRNA及蛋白的表达.乌司他丁可能通过降低TLR4水平抑制LPS诱导的炎症反应.     

The changes of hepatic sinusoidal microcirculation and effects of nitric oxide synthase inhibitor during sepsis

BACKGROUND/AIMS: Sepsis may cause changes in liver blood flow, which may result in liver injury. Microcirculation in organ undergoes moderate alteration during sepsis or septic shock. The changes in hepatic microcirculation corresponding to liver functions and the effects of nitric oxide synthase inhibitor on the liver during sepsis were studied. METHODOLOGY: Sepsis was produced by CLP (cecal ligation and two-hole puncture). In part I, the leukocyte adherence, leukocyte rolling numbers, and velocity of sinusoidal microcirculation of liver were compared with in vivo microscopy among early septic, late septic and control rats. In part II, the rats were randomly divided into two groups after CLP procedure, group A was given L-NAME (NG-nitro-L-arginine-methylester hydrochloride), 10 mg/kg BW, and group B was given normal saline as a control. The hepatic microcirculation, measured with a Laser-Doppler Flowmeter, was performed at 0, 2, 4, 6, and 8 hours after the CLP procedure. Their liver functions were also examined and compared with the microcirculation. RESULTS: The results showed that the adherent and rolling numbers of leukocytes in the sinusoidal capillary significantly increased in early and late septic rats; and the centralized velocity of flow significantly decreased in late septic rats. For rats without L-NAME, their sinusoidal flux of the liver increased 2 and 4 hours after CLP, and then decreased gradually. Their GOT levels progressively increased after CLP, but the albumin levels decreased. For rats with L-NAME (group A), their sinusoidal flux levels at 2, 4 and 6 hours after CLP were significantly lower than those in rats without L-NAME (group B), but their GOT levels were higher since the 4th hour after CLP. CONCLUSIONS: Our conclusions are that hepatic microcirculation initially increased then decreased and the liver functions deteriorated gradually after sepsis was induced. These changes were aggravated when the nitric oxide synthesis was inhibited.     

Shunting of the microcirculation after mesenteric ischemia and reperfusion is a function of ischemia time and increases mortality

OBJECTIVE: Shunting of the microcirculation contributes to the pathology of sepsis and septic shock. The authors address the hypothesis that shunting of the microcirculation occurs after superior mesenteric artery occlusion (SMAO) and reperfusion, and explore functional consequences. METHODS: Spontaneously breathing animals (rats) (n = 30) underwent SMAO for 0 (controls), 30 (SMAO_30) or 60 min (SMAO_60) followed by reperfusion (4 h) with normal saline. Leukocyte-endothelial interactions in mesenteric venules were quantified in an exteriorized ileal loop using intravital microscopy. Abdominal blood flow was recorded continuously, and arterial blood gases were analyzed at intervals. The above groups were matched by comparable groups with continuous superior mesenteric artery blood flow measurements and without exteriorizing an ileal loop (controls*, SMAO_30*, SMAO_60*). RESULTS: Adherent leukocytes increased shortly after reperfusion in ischemia groups, and plateaued in these groups. Centerline velocity in the recorded venules was significantly reduced after reperfusion down to low-flow/no-flow in SMAO_60 as compared to SMAO_30 and controls, whereas perfusion of the SMA and ileal vessels persisted. The microcirculatory changes in SMAO_60 were accompanied by progressive metabolic acidosis, substantially larger volumes of intravenous fluids needed to support arterial blood pressure and significantly reduced survival (30%). SMA blood flow increased in relation to abdominal blood flow after reperfusion in SMAO_60*, and remained constant in SMAO_30* and controls*. Survival was 80% in SMAO_60*. CONCLUSION: Shunting of the microcirculation can be observed after SMAO for 60 min and reperfusion, and contributes significantly to the pathology of mesenteric ischemia and poor outcome.     

三七总皂苷预处理对大鼠小肠缺血再灌注损伤的保护作用

目的:探讨三七总皂苷对大鼠小肠缺血再灌注(ischemia-reperfusion,IR)损伤的保护机制.方法:用肠系膜上动脉夹闭-松夹方式复制SD大鼠IR模型.检测血浆脂多糖和D-乳酸含量;取血液、肝、脾、肠系膜淋巴结,做细菌培养;免疫组织化学检测小肠组织中的NF-B及TNF-表达;用脱氧核糖核酸末端转移酶介导的缺口末端标记技术检测小肠组织细胞凋亡.结果:PNS组肝、脾、肠系膜淋巴结及血液细菌培养阳性数显著低于模型组(P<0.05);三七总皂苷200mg/kg和400mg/kgPNS组血浆脂多糖浓度分别是461EU/L,320EU/L,与模型组(570EU/L)比较差异显著(P<0.05);PNS组的血浆D-乳酸浓度分别是0.37mmol/L,0.31mmol/L,与模型组(0.44mmol/L)比较差异显著(P<0.05);三七总皂苷也可降低NF-B和TNF-的表达,且细胞凋亡数密度低于模型组.结论:三七总皂苷通过降低NF-B和TNF-表达,减轻细胞因子对小肠的损伤,减少小肠黏膜细胞凋亡,发挥对小肠IR损伤的保护作用.     

C1-esterase-inhibitor treatment at early reperfusion of hemorrhagic shock reduces mesentry leukocyte adhesion and rolling.

OBJECTIVE: Complement activation probably plays a pathogenic role in multiple organ failure in shock. This study evaluates the effects of C1-esterase-inhibitor treatment on leukocyte-endothelial interaction in the mesenteric microcirculation in hemorrhagic shock. METHODS: Rats underwent median laparotomy and exteriorization of an ileal loop for intravital microscopy of the mesenteric microcirculation. Volume controlled hemorrhagic shock was provoked by arterial blood withdrawal (2.5 mL/100 g body wt. for 60 minutes) followed by a 4-hour reperfusion period. C1-INH (100 IU/kg body wt. i.v.) or 0.9% NaCl i.v. were administered as a bolus at the beginning of reperfusion. Reperfusion time mimicked a "pre-hospital" phase of 30 minutes followed by a quasi "in-hospital" phase of 3.5 hours. The "in-hospital" phase was initiated by substitution of blood followed by fluid resuscitation with normal saline. RESULTS: Application of C1-INH markedly reduced rolling and adherent leukocytes to numbers approaching baseline values. Vmax and shear rate of the mesenteric microcirculation improved in both groups after reperfusion with a trend to higher values in the C1-INH group (n.s. p = 0.08). CONCLUSION: C1-INH applied in a bolus dose of 100 IU/kg body wt. i.v. abrogated enhanced leukocyte adhesion and rolling in the mesenteric microcirculation after hemorrhagic shock. Single bolus treatment with a complement inhibitor may provide clinical benefit when applied at an early stage of reperfusion during hemorrhagic shock.     

Terlipressin inhibits in vivo aortic iNOS expression induced by lipopolysaccharide in rats with biliary cirrhosis

In cirrhosis, lipopolysaccharide (LPS, a product of Gram-negative bacteria) in the blood may cause septic shock. LPS-elicited induction of arterial inducible nitric oxide synthase (iNOS) results in nitric oxide (NO)-induced vasodilation, which causes arterial hypotension and hyporeactivity to alpha(1)-adrenergic constrictors. In vitro studies have suggested that vasopressin inhibits iNOS expression in cultured vascular smooth muscle cells exposed to LPS. Thus, the aim of this study was to investigate the effects of terlipressin administration (a vasopressin analog) on in vivo LPS-induced aortic iNOS in rats with cirrhosis. LPS (1 mg/kg, intravenously) was administered followed by the intravenous administration of terlipressin (0.05 mg/kg, intravenously) or placebo 1 hour later. Arterial pressure was measured, and contractions to phenylephrine (an alpha(1)-adrenoceptor agonist), iNOS activity, and iNOS expressions (mRNA and protein) were investigated in isolated aortas. LPS-induced arterial hypotension and aortic hyporeactivity to phenylephrine were abolished in rats that received terlipressin. LPS-induced aortic iNOS activity and expression were suppressed in terlipressin-treated rats. In conclusion, in LPS-challenged rats with cirrhosis, terlipressin administration inhibits in vivo LPS-induced aortic iNOS expression. Terlipressin administration may be a novel approach for the treatment of arterial hypotension and hyporeactivity to alpha(1)-adrenergic constrictors in patients with cirrhosis and septic shock.     

血管活性肠肽对内毒素性休克大鼠肠道TLR4、MD2和BD3 mRNA表达的影响

目的探讨血管活性肠肽(vasoactive intestinal peptide,VIP)对细菌脂多糖(lipopolysaccharide,LPS)致休克大鼠肠道组织TLR4、MD2和BD3 mRNA表达的影响。方法 40只SD大鼠,随机分为LPS组(15只)、LPS+VIP组(15只)和对照组(10只)。LPS组尾静脉注射LPS(E.coli O55B5)10 mg/kg;LPS+VIP组尾静脉注射LPS 10 mg/kg后注射VIP 5 nmol/kg;对照组尾静脉注射等容量生理盐水。分别于注射后6 h和24 h处死,留取结肠组织标本,RT-PCR检测结肠组织TLR4、MD2和BD3 mRNA表达,光镜下观察24 h时肠组织病理变化。结果①肠组织病理改变:注射LPS后大鼠肠黏膜坏死脱落,微绒毛结构消失,结缔组织明显充血,大量的炎性细胞浸润。采用VIP治疗后病变明显减轻。②TLR4、MD2和BD3 mRNA表达:注射VIP后6 h、24 h,肠组织TLR4、MD2和BD3 mRNA表达升高(P0.05);24 h时LPS+VIP组TLR4、BD3和MD2 mRNA表达明显低于LPS组(P0.05)。结论 LPS致内毒素性休克大鼠肠道损伤时,肠组织TLR4、MD2和BD3 mRNA表达增强。VIP可减轻LPS所致肠道黏膜损伤,其机制可能与下调重要的炎症基因TLR4、MD2和BD3 mRNA表达有关。