Role of Nuclear Transcription Factor-кB in Endotoxin induced Shock in Rats

Summary: To investigate the role of NF-κB in endotoxic shock in rats, the model of endotoxin-shock rats was induced by intravenous infusion of lipopolysaccharide (LPS). 1 h, 2 h, 4 h and 6 h after LPS injection, the activation of NF-κB in blood mononuclear cells and the content of TNF-α and IL-6 in plasma was detected by enzyme-linked immunoadsordent assay (ELISA). The level of mean arterial pressure (MAP) and the histopathological changes of lung and liver were also observed. The activation of NF-κB in mononuclear cells increased 1 h after LPS injection and reached its peak 2 h after the injection, and its level was higher than that of normal group. The level of TNF-α was increased 1 h after the infusion and peaked 2 h after the injection, and its level was higher than that of normal group after LPS infusion. The content of IL-6 increased gradually with time, the IL-6 level was higher than that of normal group after LPS injection. MAP was decreased gradually with time and its level was lower than that of normal group after LPS injection. Pathological examination showed that endotoxic shock could cause pulmonary alveolar hemorrhage, edema and infiltration of inflammatory cell in lung tissue and congestion, edema, capillary dilation and inflammatory cell infiltration in liver tissue. It is concluded that NF-κB can up-regulate the expression of TNF-α and IL-6 in plasma and play an important role in endotoxin-induced shock in rats.

Cholecystokinin octapeptide improves cardiac function by activating Cholecystokinin octapeptide receptor in endotoxic shock rats

AIM: To explore the effect of sulfated cholecystokinin octapeptide (sCCK-8) on cardiac functions and its receptor mechanism in endotoxic shock (ES) rats. METHODS: The changes of the mean arterial pressure (MAP), heart rate (HR), the left ventricular pressure (LVP) and the maximal/minimum rate of LVP (±LVdp/dt max) were measured by using physiological record instrument in eight groups of rats. The expression of cholecystokinin-A receptor (CCK-AR) and cholecystokinin-B receptor (CCK-BR) mRNA of myocardium in ES rats was examined by reverse transcription polymerase chain reaction (RT-PCR). RESULTS: (1) Low doses of sCCK-8 (0.4 μg/kg) caused tachycardia (441±27, normal control 391±22 s/min) and slight increase in MAP, LVP and ±LVdp/dtmax (16.96±1.79, 18.21±1.69 and +768.85±31.28/-565.04±27.71 kPa, respectively, all P<0.01), while medium doses (4.0 μg/kg) and high doses of sCCK-8 (40 μg/kg) elicited bradycardia and marked increase in MAP, LVP and ±LVdp/dtmax (17.29±1.63, 19.46±2.57 and +831.46±22.57/-606.08 ±31.32; 17.46±1.08, 19.83±2.91 and +914.52±35.95/ -639.15±30.23 kPa, respectively, all P<0.01). Proglumide (1.0 mg/kg), a nonselective antagonist of CCK-receptor (CCK-R), significantly inhibited the pressor effects of sCCK-8 (15.96±1.38, 17.36±0.66 and +748.18±19.29/-512.12±14.39 kPa, respectively, all P<0.01), whilst reversing the bradycardiac responses. (2) High doses of LPS (8 mg/kg) elicited marked decrease in MAP, LVP and ±LVdp/dtmax. (7.16±0.59, 7.6±0.68 and +298.01±25.52/ -166.96±19.25 kPa, respectively, all P<0.01). Pretreatment with sCCK-8 (40 μg/kg) could reverse the decline of cardiac functions (10.71±0.45, 11.7±1.26 and +446.04±67.18/ -347.90±36.98 kPa, respectively, all P<0.01), while proglumide could cause further decline of cardiac function in ES rats (4.71±0.67, 5.58±1.25 and +226.48±15.84/ -142.83±20.23 kPa, respectively, all P<0.01). (3) CCK-A/BR mRNAs were expressed in myocardium of control rats. Gene expression of CCK-AR and CCK-BR significantly increased in myocardium of ES rats. The increase of CCK-AR mRNA induced by LPS began at 0.5 h, peaked at 2 h, kept a high level at 6 h and declined at 12 h, respectively. Similar to CCK-AR mRNA, the expression of CCK-BR mRNA peaked at 2 h and kept a high level at 6 h, but it did not change at the first 0.5 h and was stable at a high level at 12 h. CONCLUSION: The above results indicate that endogenous and exogenous sCCK-8 may significantly improve cardiac function and intractable hypotension of ES rats, which was likely related to high expression of CCK-A/BR in myocardium induced by LPS.

THE EFFECT OF ACUPUNCTURING ACUPOINTS ON THE CHANGE OF ELECTROENCEPHALOGRAM (EEG) IN ENDOTOXIC SHOCKED RATS

In present work,EEG and BP were used as the indexes to observe the relationbetween the change of EEG and the change of BP in the endotoxic shocked rats。At maintainingshock for 1 hr,dysrhythmia of EEG appeared in 38/46 cases.Simultaneously,there was a markeddrop in Bp,P【0.05.Following the shocked time prolonged,dysrhythmia was getting severe。AfterEA”Rengzhong"(n=14)or“Zusanli”(n=12),BP was significantly increased(P【0.05),anddysrhythmia of EEG showed clear improvement in most of the rats。There was a close relation be-tween the changes of EEG and BP,the change of EEG had a direct bearing on the change of BP.

Effect of CD11a／CD18 monoclonal antibody on the microcirculation disorder of rabbits in endotoxic shock

The CD11a/CD18 monoclonal antibody was injected into rabbits with endotoxic shock in order to observe the effect of the antibody on microcirculation. The resuh showed that the injection of CD11a/CD18 monoclonal antibody could obviously reduce the number of leukocytes adhered on the venule wall, increase the blood velocity and attenuate the falling of mean arterial pressure in the shock rabbits, which indicates that CD11a/CD18 takes part in the pathogenesis of leukocytes adherence in endotoxic shock. Blocking CD11a/CD18 can improve microcirculation to a certain extent.

EFFECTS OF METHYLENE BLUE ON THE BLOOD PRESSUREAND CGMP OF ENDOTOXIC SHOCK RABBITS

Objective To investigate the effect of methylene blue (MB) on the blood pressure and cGMP ofendotoxic shock. Methods An experiment was performed on 16 New Zealand rabbits suffering from endotoxicshock, in which 8 were distributed to the trial group (MB infusion) and another 8 to the control group (normalsaline). The mean arterial pressure (MAP), plasma cyclic monophosphate guanylate (cGMP), and arterialnatriuretic factor (ANF) in the two groups were observed. Results in the trial group MB infusion elevated MAP(P<0.01), decreased cGMP (P<0.01) and did not change the level of ANF. In the control group, normal salineinfusion did not alter MAP, plasma cGMP and ANF level. In addition, the MAP of the trial group was foundsignificantly higher than that of the control group (P<0.01) and the plasma cGMP of the trial group significantlylower than that of the control group (P<0.01). Conclusion These data suggest that the elevation of plasmacGMP is related to hypotension and MB in vivo can effectively inhibit soluable guanylate Cyclase, thus decreaseplasma cGMP level and increase MAP of rabbits with endotoxic shock. This indicates that MB can be used as adrug for the treatment of endotoxic shock.

Protective effects of bactericidal/permeability-increasing protein onrats after endotoxic shock

objective: To investigate the protective effects of bactericidal/permeability-increa protein (BPIP) on rats after endotoxic shock as to provide more experimental evidence for studies on its clinical use. Methods:E. coli 026:B6 LPS was injected at a dosage of 12. 5 mg/kg through the artery to reproduce endo toxic shock. BPIP at a dosage of 5 mg/kg (BPIP-treated group) or equal volume of normal saline (control group) were injected immediately after the injection of LPS. Results: ①Survival time of the shocked animals was prolonged and the 24 h survival rate was also significantly increased in BPIP-treated group as compared with the control group. ②The mean arterial pressure, left intraventricular systolic pressure, isovolemic ven tricular pressure and ±dp/dtmax. were significantly higher in BPIP-treated group than in control group. ③ Plasma levels of glutamic-pyruvic transaminase and urea nitrogen were markedly higher but those of endotox in and TNFα were lower in BPIP-treated group than in control group. Conclusion: BPIP can exert significant protective effects on cardiac, hepatic and renal functions in rats after endotoxic shock, indicating that BPIP might be a good choice in treatment of sepsis/septic shock.

Regulatory effects of phospholipase A_2 inhibitors on platelet activating factor in endotoxic shock in rabbits

The regulatory effects of phospholipase A2(PLA2) inhibitors, chloroquine and dexamethasone, on the activity of blood PLA2 and its related lipid mediators during endotoxic shock were observed in rabbits. The rabbits were randomized into 4 groups as follows : The normal control (NC) group consisted of 12 rabbits with sham injection . the endotoxic shork (ES) group of 31 rabbits, the chloquine pretreated (CQ) group of 16 rabbits receiving 3 mg/kg of chlorqouine and the dexamethasone-pretreated (DM) group of 10 rabbits receiving 5 mg/kg of dexamethasone. Blood was sampled before and 5 and 30 min, 1 ,3, 5 and 8 h after the administration of endotoxin for the determination of PLA2, platelet activating factor (PAF) , TXB2 and 6-keto-PGF1α. In addrtion, changes of mean arterial pressure (MAP) and respiratory rate (RR) were also carefully recorded. It was found that the activities of PLA2 and PAF and the levels of TXB2 and 6-keto-PGF1α. were significantly increased after the infusion of endotoxin. CQ and DM markedly suppressed the activities of PLA2 and PAF. The inhibition of CQ on TXB2 and 6-keto-PGF1α was greater than that of DM. Besides, CQ and DM could increase the survival rate of the animals from 48% to 75% (CQ group) and 70% (DM group). These findings suggest that PLA2 inhibitors such as CQ and DM can significantly attenuate the formation of shock mediators such as PLA2, PAF, TXB2 and 6-keto-PGF1α, and so improve the prognosis of the victims of endotoxic shock.

Effect of flunixin meglumine alone and in combination on haemodynamics during bovine endotoxic shock and after treatment

To investigate the effect of Flunixin meglumine- a NSAID;alone and in combination with hypertonic saline on endotoxemic buffalo calves, two groups of five apparently healthy male buffalo calves aged be-tween 6-8 months were subjected to I.V. infusion of E.coli endotoxin at the rate of 5μg/kg BW per hour for 3 hours. A highly significant (P < 0.01) fall in mean systolic,diastolic, pulse, mean arterial pressure (M.A.P), central venous pressure (C.V.P) and haemo-globin was observed till the end of endotoxin infusion while respiratory rate was significantly elevated along with a non-significant alteration in rectal tem-perature and hematocrit during the infusion of en-dotoxin. Immediately at the end of endotoxin infusion, flunixin meglumine at the rate of 1.1 mg/kg B.W was infused i.v. in group-I animals and group-II animals were infused with hypertonic saline solution (H.S.S.) at the rate of 4 ml/Kg BW as one time infusion fol-lowed by flunixin meglumine at the rate of 1.1 mg/kg B.W which resulted in increase of various parameters either to normal or very close to normal value while the rectal temperature and haematocrit decreased non-significantly throughout the observation period of 7 hours. No improvement in Hb and respiration was observed consequent to FM administration. Both treatments successfully raised systolic, diastolic, pulse pressure, C.V.P & M.A.P to normal pre-infusion val-ues. From the results of the present investigation, it can be concluded that i.v. infusion of FM alone and in combination with hypertonic saline solution in en-dotoxemic buffalo calves effectively restores the various hemodynamic parameters close to normal pre-infusion values and it can be used as immediate resuscitation measure to provide the clinician valu-able time to plan further long term treatment.

Gene Delivery of SOCS3 Protects Mice from Lethal Endotoxic Shock

Suppressor of cytokine signaling 3 （SOCS3） was reported as a feedback inhibitor of cytokine receptor signaling by inhibiting the JAK-STAT signal transduction pathway. We sought to test the anti-endotoxic septic shock effect of liposome mediated gene delivery of SOCS3 in a lethal endotoxic shock mouse model. BALB/c mice were injected intraperitoneally with 200μg pcDNA3.1-SOCS3 cationic liposomes, while pcDNA3.1-IL-10 and empty vector as positive and negative control respectively. Forty-eight hours after gene delivery, mice were challenged with 4 μg of E.coli 0127：B8 LPS and 18 mg D-GaIN administered i.p. 90 min later, serum TNF-α level was determined. Survival over the next 48 h was evaluated. Peritoneal macrophages from survival mice were stimulated in vitro with 1 μg/ml LPS for 18 h, and the supernatants were harvested for determination of the amount of TNF-α. We found that gene delivery of SOCS3 significantly increase the mouse survival rate from 27.8 ± 9.6% of control group to 61.1 ± 9.6% （p 〈 0.01）. In comparison with control group （218 ± 13 pg/ml） and sham delivery group （219 ± 22 pg/ml）, gene delivery of SOCS3 reduced the level of serum TNF-α （68 ± 9 pg/ml） significantly （p 〈 0.01）. Furthermore, gene delivery of SOCS3 displayed the capacity of prevention of tolerance of peritoneal macrophages to LPS. These findings suggest that gene delivery of SOCS3 mediated by liposome is a promising approach for endotoxic septic shock treatment. Cellular ＆ Molecular Immunology.

木犀草素通过调节细胞凋亡和炎症发挥对内毒素性所致急性肾损伤的保护作用

目的探讨木犀草素对急性肾损伤的保护作用。方法通过脂多糖(LPS构建小鼠内毒素性所致的急性肾损伤模型,使用木犀草素对肾损伤小鼠进行治疗;给小鼠尾静脉注射miR-30c-5p antagomir以敲低miR-30c-5p的表达。动物分组如下:正常对照组、LPS组、木犀草素治疗组(LPS+Lu组)、木犀草素治疗的阴性对照组(LPS+DMSO组)、miR-30c-5p表达敲低组(antagomir 30c-5p组)、miR-30c-5p表达敲低对照组(antagomir NC组)。采用自动化学分析仪测定小鼠血清肌酐和尿素氮水平,通过HE染色观察肾组织病理损伤。采用ELISA试剂盒检测小鼠血清胱抑素C(Cys-C)、肿瘤坏死因子(TNF)-α、白细胞介素(IL)-6、IL-4水平,通过TUNEL染色和Western blot检测细胞凋亡。结果与正常对照组相比,LPS组小鼠急性肾损伤病理情况严重,血清肌酐、尿素氮和Cys-C、促炎因子IL-6、TNF-α、促凋亡因子B淋巴细胞瘤-2基因(Bcl-2)相关X蛋白(Bax)的表达水平显著升高(P<0.05),而抗炎因子IL-4、抗凋亡因子Bcl-2、miR-30c-5p水平显著下降(P<0.05)。与LPS组相比,LPS+Lu组肾损伤病理情况减轻,血清肌酐、尿素氮和Cys-C、IL-6、TNF-α、Bax的表达水平显著降低,而IL-4、Bcl-2、miR-30c-5p水平显著上升(P<0.05)。与antagomir NC组小鼠相比,antagomir 30c-5p组小鼠促炎因子水平及细胞凋亡率显著上升(P<0.05)。结论木犀草素通过上调miR-30c-5p表达抑制炎症和细胞凋亡从而保护急性肾损伤小鼠。

参附注射液对兔内毒素休克肺损伤的保护作用

用兔内毒素（ＥＴ）休克模型，对平均动脉压（ＭＡＰ）及支气管肺泡灌洗液（ＢＡＬＦ）中蛋白含量及吞噬细胞（ＰＡＭ）变化进行观测，探讨参附注射液（ＳＦ）对兔内毒素休克肺损伤的作用。结果：ＥＴ＋ＳＦ组ＭＡＰ虽下降，但２ｈ后开始上升，至６ｈ基本恢复正常，其与ＥＴ组比，Ｐ＜０．０５，与假手术组（Ｓｈａｍ组）比，ＥＴ２ｈ后差异无显著性；对ＢＡＬＦ中细胞总数和ＰＭＮ，ＥＴ＋ＳＦ组与ＥＴ组比较，差异显著（Ｐ＜０；０１）；蛋白定量，ＥＴ＋ＳＴ组与ＥＴ组间差异显著（Ｐ＜０．０５），而与Ｓｈａｍ组间差异不显著（Ｐ＞０．０５），证明参附注射液对肺损伤有明显的保护作用。

大黄抗内毒素性休克大鼠炎性介质作用的实验研究

目的：研究大黄对内毒素性休克大鼠炎性介质作用的机制。方法：选用大鼠内毒素性休克模型。随机分为６组：单纯手术组、内毒素组、大黄预防用药组（１５０ｍｇ／ｋｇ组和７５０ｍｇ／ｋｇ组）和大黄治疗组（１５０ｍｇ／ｋｇ组和７５０ｍｇ／ｋｇ组）。检测磷脂酶Ａ２（ＰＬＡ２）和血小板活化因子（ＰＡＦ）的活性。结果：内毒素注射前６组大鼠平均动脉压（ＭＡＰ）无显著性差异；注射内毒素后４小时ＭＡＰ明显降低；大黄预防用药组和大黄治疗组ＭＡＰ则与注射内毒素前及单纯手术组比较均无明显变化，并均显著高于内毒素组注射内毒素４小时后。注射内毒素后４小时，血清和小肠组织中ＰＬＡ２活性及ＰＡＦ含量均明显增高；与内毒素组注射内毒素后４小时比较，大黄预防组和治疗组则血清和小肠组织中ＰＬＡ２活性和ＰＡＦ含量显著降低。

山羊内毒素休克诱发脂质过氧化作用及山莨菪碱对其影响的研究

本文将３０头杂交山羊分成３组，第１组（ｎ＝６）为对照组，第２组（ｎ＝１２）静注大肠杆菌内毒素复制休克模型，第３组（ｎ＝１２）在第２组基础上提前１０ｍｉｎ静注山莨菪碱注射液，检测１２ｈ内不同时间血清丙二醛（ＭＤＡ）含量、总ＳＯＤ、Ｍｎ－ＳＯＤ、ＣｕＺｎ－ＳＯＤ、ＣＡＴ和血液ＧＳＨ－Ｐｘ活性。结果表明：第２组血清ＭＤＡ含量明显增加（Ｐ＜０．０１），血清Ｔ－ＳＯＤ、Ｍｎ－ＳＯＤ、ＣｕＺｎ－ＳＯＤ、ＧＳＨ－Ｐｘ、ＣＡＴ活性均显著降低（Ｐ＜０．０１），而第３组血清ＭＤＡ含量虽比第１组增加，至７ｈ后则无显著差异，并与第２组差异明显（Ｐ＜０．０１），各类抗氧化酶的活性比第２组下降幅值明显减小。提示脂质过氧化损伤在内毒素休克发生发展中起一定作用，应用６５４－２可降低脂质过氧化作用而有效地保护细胞功能和结构正常。

连续性静-静脉血液滤过对内毒素休克羊血流动力学的影响

目的 探讨连续性静静脉血液滤过( CVVH)对内毒素休克血流动力学的影响及作用机制,并观察其对内毒素休克预后的影响。方法 利用大肠杆菌内毒素( L 2 880 )诱导绵羊内毒素休克模型,随机分为对照组( NHF)和治疗组( HF)两组,观察CVVH(零平衡,40 ml·kg-1·h-1超滤,血流速80 ml/ min)对内毒素休克羊血流动力学的影响。结果 内毒素注入后两组实验动物平均动脉压( MAP)明显下降;平均肺动脉压( MPAP)、心脏指数( CI)显著升高( P<0 .0 1或P<0 .0 5)。实施CVVH后,HF组MAP、每搏量( SV)明显上升,显著高于NHF组( P<0 .0 1或P<0 .0 5) ;HF组CI无明显变化,NHF组进行性下降并显著低于HF组( P<0 .0 5) ;两组MPAP差异无显著性( P>0 .0 5) ;血浆乳酸浓度NHF组明显高于HF组。5h后HF组全部存活,NHF组死亡2只。结论 应用大肠杆菌内毒素静脉注射可成功制备羊内毒素休克模型;CVVH具有改善内毒素休克血流动力学和预后的作用,是治疗内毒素休克的重要手段。

牛珀至宝丹对内毒素休克大鼠血液流变学的影响

目的：探讨牛珀至宝丹抗内毒素休克的作用机制。方法：采用静注致死量灭活大肠杆菌内毒素造成大鼠重症感染性休克模型，以牛珀至宝丹预先处理动物（实验组），并与正常组、内毒素体克组进行对照观察。结果：实验组血压下降幅度显著低于休克组；血液流变学指标中全血粘度、血浆比粘度、红细胞聚集指数、红细胞刚性指数和红细胞压积实验组较休克组均明显降低，红细胞电泳时间缩短；与正常组比较无显著性差异（Ｐ＞０．０５），但与休克组比较有显著性差异（Ｐ＜０．０５或＜０．０１）。结论：牛珀至宝丹能明显改善内毒素休克大鼠血液流变性，并对内毒素休克大鼠有一定的升压作用。

新生大鼠内毒素休克时血清TNF-α和NO对心肌超微结构的影响(英文)

目的观察新生大鼠内毒素休克时血清TNF-α和NO的动态变化以及与心肌细胞损害的关系,探讨地塞米松(DXM)对心肌的保护作用。方法健康7 d Wistar大鼠17只,随机取9只作实验前基础值组,余108只随机分成对照组、休克组(LPS 5 mg/kg)及治疗组(LPS 5 mg/kg+DXM 5 mg/kg)。各组于注射LPS前(0 h)及注射后2,4,6,24 h分别断头取血并留取心脏组织。双抗夹心ELISA方法测定血清TNF-α浓度,硝酸盐还原酶法测定血清NO浓度,以透射电镜观察心肌超微结构改变。结果①休克组TNF-α于注射LPS2 h达高峰,6 h后下 降到对照组水平。注射LPS 2 h后,DXM组TNF-α高于对照组(P<0.05),但明显低于休克组(P<0.05);注射LPS 4 h,DXM组TNF-α含量低于休克组(P<0.05),但与对照组差异无显著性(P>0.05)。LPS注射后6 h起,3组问TNF-α差异均无显著性(P>0.05)。②休克组血清NO从注射LPS 2 h起升高(P<0.01),24 h达高峰(P<0.01);从注射LPS 2 h起,DXM组血清NO均低于同时间点休克组(P<0.01)。③心肌超微结构改变:休克组于注射LPS 6 h心肌细胞少数线粒体有空泡变性,24 h出现心肌纤维断裂、大量线粒体空泡变性、坏死。而DXM组在注射LPS24 h仅少数线粒体有空泡变性,心肌纤维完整。结论内毒素休克新生大鼠通过释放炎症介质损害心肌组织。

山莨菪碱对山羊内毒素休克时肝脏自由基损伤的保护机理

将３６头杂交山羊随机分成３组：Ⅰ组作为对照；Ⅱ组静注大肠杆菌内毒素１８００ＥＵ／ｋｇ，注射２次，间隔２４ｈ；Ⅲ组在同Ⅱ组处理基础上，于第２次注射前１０ｍｉｎ静注山莨菪碱（６５４－２）注射液２．５ｍｇ／ｋｇ。第２次注射内毒素后５ｈ和１２ｈ各组均剖杀６头山羊，检测肝脏抗氧化系统功能。结果表明：Ⅱ组肝组织丙二醛（ＭＤＡ）含量明显高于Ⅰ组（Ｐ＜０．０５），谷胱甘肽过氧化物酶（ＧＳＨ－Ｐｘ）和谷胱甘肽还原酶（ＧＲ）活性及总超氧化物岐化酶（Ｔ－ＳＯＤ）、Ｍｎ－ＳＯＤ活性显著降低（Ｐ＜０．０１，Ｐ＜０．０５），同时肝组织还原型谷胱甘肽（ＧＳＨ）、总巯基（Ｔ－ＳＨ）、非蛋白巯基（ＮＰ－ＳＨ）和蛋白结合巯基（ＰＢ－ＳＨ）含量下降（Ｐ＜０．０５）。而Ⅲ组肝组织ＭＤＡ含量于５ｈ时与Ⅰ组无显著差异（Ｐ＞０．０５），１２ｈ明显低于Ⅱ组（Ｐ＜０．０５），ＧＳＨ－Ｐｘ和ＧＲ活性在５ｈ下降不显著，ＧＲ活性至１２ｈ高于Ⅱ组（Ｐ＜０．０５），Ｔ－ＳＯＤ、ＣｕＺｎ－ＳＯＤ活性和ＧＳＨ、Ｔ－ＳＨ、ＮＰ－ＳＨ、ＰＢ－ＳＨ含量均显著高于Ⅱ组（Ｐ＜０．０５）。提示山羊内毒素休克时肝脏产生明显的氧自由基诱导的脂质过氧化损伤，提前注射６５４－２能够有效地减?

脂多糖诱导小鼠脏器中胞间粘附分子-1的表达

为研究脂多糖 (lipopolysaccharide,LPS)诱导的内毒素休克小鼠多种脏器中胞间粘附分子 1(intercellularadhesionmolecule 1,ICAM 1)表达的差异 ,用 5mg/kgLPS腹腔注射小鼠后 ,分别采用Westernblotting和RT PCR法检测组织中ICAM 1蛋白和mRNA的表达情况。结果显示 ,在正常小鼠 ,ICAM 1蛋白和mRNA的表达在肺中最多 ,其次是脾脏 ,在肾脏和肠有少量表达 ,在肝脏和心脏中未能检出。LPS腹腔注射后 6h可诱导小鼠发生内毒素休克 ,此时 ,ICAM 1蛋白表达仍以在肺中最多 ,在肝、脾、心、肾和肠依次减少 ;其中在肺、肾和脾分别比正常时增加 4 5、3 0和 1 5倍 ,而且在正常时不能检出的肝和心中呈现阳性 ,但在肠中则变化不大。脏器中ICAM 1mRNA亦相应显著增加。上述结果表明 ,在LPS诱导的内毒素休克小鼠的多种脏器中ICAM 1蛋白和mRNA表达显著增加。脏器间ICAM 1表达上调的差异可能带来内毒素休克时脏器的不同易伤性 ,抑制ICAM 1的表达可能对内毒素休克的防治有重要的意义。

牛珀至宝丹对内毒素休克大鼠溶酶体的保护作用

目的：探讨中药制剂牛珀至宝丹对内毒素休克大鼠溶酶体的保护作用。方法：用ＳＤ大鼠制作休克模型并同期对大鼠肝溶酶体进行体内外稳膜实验，以溶酶体标志酶——酸性磷酸酶（ＡＣＰ）的活性、酶比活性、溶酶体膜通透率等反应肝溶酶体的变化，以观察牛珀至宝丹对肝细胞溶酶体的影响。结果：模型组游离ＡＣＰ活性为（１１０．１９±４．３３）ｎｍｏｌ·ｓ－１／ｇ，膜通透率为０．８４±０．０３；而牛珀至宝丹组分别为（８３．５２±８．１７）ｎｍｏｌ·ｓ－１／ｇ和０．６４±０．０８，２组比较均有显著性差异（Ｐ均＜０．０１）。结论：内毒素休克大鼠肝溶酶体膜明显受损，膜通透率增加，ＡＣＰ外逸；牛珀至宝丹可阻止上述变化，对溶酶体具有保护作用。

一氧化氮合酶对早期内毒素休克猕猴肾脏的影响

目的探讨早期内毒素休克肾脏损伤的发病机制。方法猕猴11只,随机分成两组:对照组5只静脉注射生理盐水;实验组6只,静脉注射脂多糖(LPS)2.8mg/kg。LPS攻击后120min,处死动物,取肾脏标本,用免疫组化方法卵白素生物素过氧化物酶法(ABC法)进行内皮型一氧化氮合酶(eNOS)和诱导型一氧化氮合酶(iNOS)染色,观察eNOS和iNOS在早期猕猴内毒素休克肾脏中的表达,同时观察肾脏超微结构的改变、酸性磷酸酶(ACP)活性变化。结果LPS攻击后120min,可见肾脏组织超微结构明显破坏和细胞内溶酶体数量增加。实验组iNOS在肾小球血管内皮、肾小管上皮、肾小球血管内和肾小管周围均有表达,对照组无表达。eNOS在实验组和对照组的肾小球血管内皮及周围血管内皮细胞均有表达。结论一氧化氮在猕猴内毒素休克早期肾脏损伤中发挥了重要作用。