人参二醇组皂苷对感染性休克大鼠血液流变性及微循环的影响

目的 观察人参二醇组皂苷(PDS)对感染性休克大鼠血液流变性及微循环的影响,探讨其抗感染性休克的作用机制.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(S组);内毒素休克模型组(L组);地塞米松预治疗组(LD组);PDS预治疗(22.5 mg/kg,LP_小)(45 mg/kg,LP_中)(90 mg/kg,LP_大)组.各组于休克后观察肠系膜微循环的变化,2 h和4 h腹主动脉取血,测量全血黏度.结果 模型组在休克2 h、4 h全血黏度明显高于PDS各剂量组(P＜0.01).肠系膜微循环的变化:PDS各剂量组在休克2～4 h微动脉管径、微动脉血流速度及微动脉管袢数均高于模型组(P＜0.05).结论 PDS通过降低内毒素休克大鼠全血黏度,改善微循环状态,起到抗休克的作用.     

脑泰方提取物对局灶性脑缺血大鼠血浆TXB_2及6-Keto-PGF_(1α)含量的影响

目的探讨大鼠局灶性脑缺血后脑泰方对其血浆血栓素B2(TXB2)及6-酮-前列腺素F1α(6-Keto-PGF1α)含量的影响。方法线栓大鼠左侧大脑中动脉制作大鼠局灶性脑缺血模型,65只健康SD大鼠随机分为正常对照组、假手术组、模型组和脑泰方组。动态观察脑泰方治疗后1d、3d、5d和7d血浆TXB2和6-Keto-PGF1α含量的变化。结果模型组术后1d、5d、7d血浆TXB2含量和TXB2/6-Keto-PGF1α比值明显高于假手术组(P0.01),与模型组同时点比较,脑泰方组血浆TXB2含量和TXB2/6-Keto-PGF1α明显降低。结论脑泰方能通过降低血浆TXB2及TXB2/6-Keto-PGF1α,达到对局灶性脑缺血大鼠的神经保护作用。     

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。     

中医“热毒血瘀证”模型大鼠血管内皮损伤及血小板功能障碍研究

目的 研究具有中医"热毒血瘀证"表征的大鼠血管内皮细胞(VEC)损伤和血小板功能的病理变化,以阐释中医"热毒血瘀证"的现代生物医学基础.方法 大鼠腹腔注射内毒素即脂多糖(LPS),连续8周,在不同时间点进行行为学分析、检测舌血氧饱和度基础上,检测血浆内皮素(ET)、热休克蛋白-70(HSP70)、血栓烷B2(TXB2)和6-酮-前列腺素(6-Keto-PGF1α)的变化.结果 注射毒素后大鼠活动减少,舌血氧饱和度降低.早期血浆ET、HSP70和TXB2 /6-Keto-PGF1α增高,晚期TXB2/6-Keto-PGF1α降低.结论 具有舌体组织血氧饱和度下降的中医"热毒血瘀证"存在血管内皮细胞损伤及血小板功能障碍,VEC损伤在中医"热毒血瘀证"发展过程可能起着重要作用.     

氢化可的松治疗急性胰腺炎肺损伤的实验研究

目的探讨氢化可的松对实验性急性坏死性胰腺炎(ANP)肺损伤的治疗作用及作用机制.方法 54只健康SD大鼠随机分为3组:假手术(SO)组、ANP组及氢化可的松治疗.采用胰胆管逆行注射5%牛磺胆酸钠(1 ml/kg体重)诱导大鼠ANP模型.氢化可的松治疗组于型制作成功后10 min给予舌下静脉注射氢化可的松(10 mg/kg体重).各组于术后3 h、6 h和12 h分批处死动物,观察各组大鼠血浆淀粉酶、TNF-α、IL-6、血栓素B2(TXB2)、6酮前列腺素F1α(6-Keto-PGF1α)、TXB2/6-Keto-PGF1α比值、肺组织髓过氧化物酶(MPO)、肺湿干比值及胰腺、肺组织病理变化.结果 ANP组血浆淀粉酶、TNF-α、IL-6、TXB2、TXB2/6-Keto-PGF1α比值、肺组织MPO均较SO组明显升高(P < 0.05),6 h、12 h肺湿干比值较SO组明显升高(P < 0.01);氢化可的松治疗组TNF-α、IL-6、TXB2、TXB2/6 Keto PGF1α比值、肺组织MPO均较ANP组显著降低(P < 0.05),6 h、12 h肺湿干比值较ANP组明显降低(P < 0.01),肺组织病理损伤较ANP组明显减轻.结论氢化可的松可减少TXA-2、TNF-α、IL-6等炎症因子的产生而对ANP肺损伤具有重要的保护作用.     

益气活血解毒法对溃疡性结肠炎复发患者血浆血栓烷B2和6-酮-前列腺素F1α水平及比值的影响

[目的]探讨益气活血解毒法对溃疡性结肠炎(UC)复发患者血浆血栓烷B2(TXB2)和6-酮-前列腺素F1α(6-Keto-PGF1α)水平及TXB2/6-Keto-PGF1α比值的影响.[方法]90例UC复发患者随机分为2组,各45例,治疗组给予益气活血解毒立法的中药汤剂,对照组给予柳氮磺吡啶(SASP)治疗,治疗前后分别检测血浆TXB2、6-Keto-PGF1α水平.[结果]治疗前UC患者血浆TXB2、6-Keto-PGF1α水平及TXB2/6一Keto-PGF1α比值均高于正常人(P<0.01);复发者血浆TXB2、6-Keto-PGF1α水平及TXB2/6-Keto-PGF1α比值均高于未复发者(P<0.01,<0.05).治疗组治疗后、随访时血浆TXB2、6-Keto-PGF1α水平及TXB2/6一Keto-PGF1α比值均低于对照组(P<0.01,<0.05).[结论]以益气活血解毒立法的中药对UC复发治疗,与SASP比较,可有效降低血浆TXB2、6-Keto-4-PGF1α水平及TXB2/6-Keto-PGF1α比值,从而阻抑血小板活化,可能是抗UC复发作用机制之一.     

胃乐散对大鼠溃疡组织TXA2、PGI2 及COX-2含量的影响及意义

目的 观察胃乐散对大鼠实验性溃疡血栓素A2(TXA2)和前列腺素I2( PGI2)及环氧合酶2(COX-2)的影响,并探讨其作用机理.方法 SD大鼠48只,随机分为正常对照组、模型组、胃乐散低剂量组、胃乐散中剂量组、胃乐散高剂量组和雷尼替丁组.采用冰醋酸烧灼法制备大鼠胃溃疡模型,连续用药后第14天处死大鼠,取溃疡部位组织提取蛋白.用ELISA法检测组织中血栓素B2(TXB2)和6-酮-前列腺素F1α(6-Keto-PGF1α)的水平变化,并观察TXB2/6-Keto-PGF1α的比值变化.Western blot检测组织中COX-2的含量.结果 与正常对照组比较,模型组6-Keto-PGF1α、COX-2水平降低(P＜0.05),TXB2及TXB2/6-Keto-PGF1α升高(P＜0.05);胃乐散高剂量组6-Keto-PGF1α的含量高于正常对照组(P＜0.05).与模型组比较,胃乐散中、高剂量组及雷尼替丁组6-Keto-PGF1α、COX-2的含量增加,特别是胃乐散高剂量组增加更为明显(P＜0.01),胃乐散高剂量组及雷尼替丁组TXB2低于模型组(P＜0.05),特别是TXB2/6-Keto-PGF1α降低更为显著(P＜0.01).结论 胃乐散治疗胃溃疡可能是通过促进PGI2分泌,纠正TXA2/PGI2的失衡来实现的.     

氢化可的松治疗急性胰腺炎肺损伤的实验研究

目的探讨氢化可的松对实验性急性坏死性胰腺炎(ANP)肺损伤的治疗作用及作用机制。方法54只健康SD大鼠随机分为3组:假手术(SO)组、ANP组及氢化可的松治疗。采用胰胆管逆行注射5%牛磺胆酸钠(1 ml/kg体重)诱导大鼠ANP模型。氢化可的松治疗组于型制作成功后10 min 给予舌下静脉注射氢化可的松(10 mg/kg体重)。各组于术后3 h、6 h和12 h分批处死动物,观察各组大鼠血浆淀粉酶、TNF-α、IL-6、血栓素B2(TXB2)、6酮前列腺素F1α(6-Keto-PGF1α)、TXB2/6-Keto-PGF1α比值、肺组织髓过氧化物酶(MPO)、肺湿干比值及胰腺、肺组织病理变化。结果ANP组血浆淀粉酶、TNF-α、IL-6、TXB2、TXB2/6-Keto-PGF1α比值、肺组织MPO均较SO组明显升高(P<0.05),6 h、12 h肺湿干比值较SO组明显升高(P<0.01);氢化可的松治疗组TNF-α、IL-6、TXB2、TXB2/6 Keto PGF1α比值、肺组织MPO均较ANP组显著降低(P<0.05),6 h、12 h肺湿干比值较ANP组明显降低(P<0.01), 肺组织病理损伤较ANP组明显减轻。结论氢化可的松可减少TXA-2、TNF-α、IL-6等炎症因子的产生而对ANP肺损伤具有重要的保护作用。     

人参二醇皂苷对失血性休克-内毒素二次打击大鼠肺组织一氧化氮含量的影响

目的探讨失血性休克复合内毒素二次打击大鼠肺组织一氧化氮（NO）含量的变化及人参二醇皂苷（PDS）对其影响。方法利用失血性休克对Wistar大鼠制造首次打击，给予地塞米松（Dex）或PDS预治疗，之后腹腔注入脂多糖（LPS）进行第二次打击，二次打击6h后处死大鼠，取肺脏组织进行一氧化氮合酶（NOS）、诱导型NOS（iNOS）活力和NO代谢产物NO2^-／NO3^-含量的测定。结果二次打击的大鼠肺脏组织NOS、iNOS活力水平及N02-／N03-均明显高于假手术对照组（P〈0．05），而经过Dex或PDS处理的大鼠肺脏组织NOS、iNOS活力水平及NO2^／NO3^-与二次打击大鼠相比均明显降低（P〈0．05）。结论失血-内毒素二次打击时，NO产生过多可能参与了急性肺损伤的发生，PDS可通过抑制NO的产生从而达到保护肺脏的作用。     

逐瘀通脉胶囊对脑梗死患者血清血管内皮细胞因子的影响

目的观察逐瘀通脉胶囊对脑梗死患者血清血管内皮细胞因子的影响。方法选择脑梗死患者120例,随机分为对照组60例和治疗组60例。对照组常规对症药物治疗基础上,加阿司匹林口服0.25mg,3次/d,连续治疗1个月。治疗组在对照组治疗的基础上,口服逐瘀通脉胶囊0.4g,3次/d,连续治疗1个月。观察2组血清血管内皮细胞相关因子血栓素B2(TXB2)、6-酮-前列腺素F1α(6-Keto-PGF1α)、NO、活性氧水平变化。结果治疗组和对照组治疗后血清TXB2、活性氧水平明显低于治疗前,6-Keto-PGF1α、NO水平明显高于治疗前(P0.05)。与对照组比较,治疗组治疗后血清TXB2、活性氧水平明显降低[(76.95±23.97)ng/Lvs(93.54±30.71)ng/L,(329.58±49.77)mmol/L vs(374.12±52.01)mmol/L,P0.05],6-Keto-PGF1α、NO水平明显升高[(113.84±36.11)ng/L vs(92.94±33.75)ng/L,(97.44±20.71)mmol/L vs(81.74±23.67)mmol/L,P0.05]。治疗组和对照组治疗后TC、LDL-C、TG、高敏C反应蛋白明显降低,HDL-C水平明显升高,且治疗组疗效明显优于对照组(P0.05)。结论逐瘀通脉胶囊可有效的降低TXB2、活性氧水平,提高6-Keto-PGF1α、NO水平,调节血脂、高敏C反应蛋白。     

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.     

Effects of in vivo pentoxifylline treatment on survival and ex vivo vascular contractility in a rat lipopolysaccharide shock model.

Depending on the dose and dosing, pentoxifylline (PTX) treatment can improve or worsen survival from lipopolysaccharide (LPS) shock in rats. Intraperitoneal (i.p.) PTX, 20 mg/kg, administered once 15 min after intravenous (i.v.) LPS (17 mg/kg), significantly improved survival in unanesthetized LPS-shocked rats. Multiple 20 mg/kg PTX injections (five total, spaced at 45 min intervals starting 15 min after LPS) significantly worsened survival. A lower dose, 12 mg/kg, given as a single or multiple injections, did not alter survival. We tested the ex vivo contractile response to norepinephrine (NE) of aortic rings isolated 3.75 hr after i.v. injection of PBS or LPS. Both untreated LPS-shocked and multiple 12 mg/kg PTX treated normal rats (i.v. PBS) had significantly diminished maximum contractility. The ex vivo vascular hypocontractility found in untreated LPS-shocked rats was not aggravated nor ameliorated by multiple 12 mg/kg PTX injections. The ex vivo effects on contractility of multiple 20 mg/kg PTX treatment of LPS shock could not be studied because survival times were shorter than 3.5 hr. In using PTX to treat LPS shock, potentially harmful vasodilation must be considered.     

Increased heat shock protein 70 expression in the pancreas of rats with endotoxic shock

AIM: To investigate the ultra-structural changes and heat shock protein 70 (HSP70) expression in the pancreas of rats with endotoxic shock and to detect their possible relationship. METHODS: A total of 33 Wistar rats were randomly divided into three groups: control group (given normal saline), small dose lipopolysaccharide (LPS) group (given LPS 5 mg/kg) and large dose LPS group (given LPS 10 mg/kg). Pancreas was explanted to detect the ultra-structural changes by TEM and the HSP70 expression by immunohistochemistry and Western blot. RESULTS: Rats given small doses of LPS showed swelling and loss of mitochondrial cristae of acinar cells and increased number of autophagic vacuoles in the cytoplasm of acinar cells. Rats given large doses of LPS showed swelling, vacuolization, and obvious myeloid changes of mitochondrial cristae of acinar cells, increased number of autophagic vacuoles in the cytoplasm of acinar cells. HSP70 expression was increased compared to the control group (P<0.05). CONCLUSION: Small doses of LPS may induce stronger expression of HSP70, promote autophagocytosis and ameliorate ultra-structural injuries.     

Association Between Heat Stress Protein 70 Induction and Decreased Pulmonary Fibrosis in an Animal Model of Acute Lung Injury

The hyperthermia-induced activation of the stress protein response allows cells to withstand metabolic insults that would otherwise be lethal. This phenomenon is referred to as thermotolerance. Heat shock protein 70 (HSP70) has been shown to play an important role in this hyperthermia-related cell protection. HSP70 confers protection against cellular and tissue injury. Our objective was to determine the effect of heat stress on the histopathology of pulmonary fibrosis caused by the administration of lipopolysaccharide (LPS) in Wistar rats. The rats were randomly divided into three groups. In the control group, rats were heated to 42°C for 15 min. In the LPS group, rats were given LPS in 0.9% NaCl solution (10 mg/kg body weight). In the WH (whole-body hyperthermia) +LPS group, rats were heated to 42°C for 15 min, and 48 h later they were injected with LPS dissolved in a 0.9% NaCl solution (10 mg/kg body weight). We investigated lung histopathology and performed a Northern blot analysis daily. Hyperthermia was shown to reduce tissue injury caused by the administration of LPS. Pulmonary tissue HSP70 mRNA was found to be elevated at 3 h after heating. HSP70 protein levels in the serum increased after whole-body hyperthermia. However, neither the expression of HSP47 mRNA nor the expression of type I or type III collagen mRNA was induced by the administration of LPS after whole-body hyperthermia. These data indicate that thermal pretreatment is associated with the induction of HSP70 protein synthesis, which subsequently attenuates tissue damage in experimental lung fibrosis.     

Dexamethasone and indomethacin treatment during endotoxicosis in the suckling rat

Gram negative sepsis/septic shock continues to be a major cause of morbidity and mortality in newborns. We studied the effects of anti-inflammatory drugs, indomethacin (IND) and dexamethasone (DX), on glucoregulation, body weight, and mortality in 10-day-old suckling rats administered Salmonella enteritidis lipopolysaccharide (LPS). IND (1.5 mg/kg) or DX (4 mg/kg) was intraperitoneally (ip) administered immediately after highly lethal LPS injection. Both IND and DX attenuated the LPS-induced hypoglycemia and lactacidemia, and decreased the mortality, IND did not alter body weight changes in rats with septic shock. DX continued a catabolic state and reduced their body weights. In rats fasted for 24 hr before LPS injection, DX, but not IND, increased the mortality. We concluded that IND and DX improved the LPS-induced glucose dyshomeostasis and decreased the mortality of endotoxic shock in 4-hr-fasted 10-day-old rats. Per contra, DX was detrimental in 24-hr-fasted 10-day-old endotoxic rats.     

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。     

Pretreatment with FK506 improves survival rate and gas exchange in canine model of acute lung injury

The novel effects of FK506 on shock induced by lipopolysaccharide and phorbol myristate acetate (LPS/PMA) were studied using beagles. Five groups were studied: endotoxin shock control group (both 0.5 mg/kg of LPS and 30 microg/kg of PMA, n = 6); methylprednisolone-treated endotoxin shock group (n = 5); FK506-treated endotoxin shock groups in which intravenous infusions of FK506 at 2.5 microg/kg/h (low dose, n = 5), 8 microg/kg/h (medium dose, n = 5), and 25 microg/kg/h (high dose, n = 5) were administered. In the control group, the survival rate was 33%. Also, arterial hypoxemia, systemic hypotension, and marked increases in pulmonary vascular resistance (PVR) and wet-to-dry weight ratio (W/D) were observed. FK506 treatment at both medium and high doses significantly attenuated these LPS/PMA-induced physiological changes, and the survival rates were 80 and 100%, respectively. On the other hand, in the methylprednisolone group, no obvious effects were observed. The present study suggests that FK506 could have prophylactic potential against acute lung injury in endotoxin shock.     

银杏叶提取物对脂多糖诱导D-半乳糖致衰老大鼠急性肺损伤的保护作用

目的　观察脂多糖 (LPS)诱导D 半乳糖 (D gal)致衰老大鼠急性肺损伤 (ALI)及银杏叶提取物 (GBE)对其是否有保护作用。方法　大鼠 2 4只随机分成两部分 ,6只为正常对照组 ;18只经腹腔注D gal复制衰老动物模型。后者再随机分成三组 :衰老对照组 (6只 ) ;LPS组 (6只 ,静脉注射LPS诱导形成ALI) ;GBE +LPS组 (6只 ,注LPS前 7天开始每天灌胃给GBE一次 ,按所含黄酮甙计算 ,8mg/kg体重 ,实验当日在给LPS前 2h再给一次GBE)。注LPS后 2h收集标本待测。结果　D gal致衰老大鼠较正常大鼠血中超氧化物歧化酶 (SOD)及肺组织Na+ K+ ATPase活性均显著降低 (P均 <0 0 5 ) ,而血中乳酸脱氢酶 (LDH)活性升高 (P <0 0 5 )。衰老大鼠注LPS后 2h已形成ALI。肺间质及肺泡中有较多炎性细胞 ;肺泡灌洗液中蛋白含量及肺通透指数增加 ;血中乳酸 (LD) ,丙二醛 (MDA) ,一氧化氮 (NO) ,内皮素 1(ET 1) ,肿瘤坏死因子 α(TNF α)含量和LDH活性以及肺组织中髓过氧化物酶 (MPO)活性 ,均显著升高 ;而血中超氧化物歧化酶活性及肺组织Na+ K+ ATPase活性均下降 (P <0 0 5 ,P <0 0 1)。预先给予GBE可显著地缓解除SOD活性外的上述其它指标的变化 (P <0 0 5 )。结论　D gal致衰老大鼠体内抗氧化能力降低。静注LPS可引起衰老大鼠明显的A     

Anti—inflammatory effect of cholecystokinin and its signal transduction mechanism in endotoxic shock rat

AIM：To study the anti-inflammatory effects of choecystokinin-octapeptide(CCK-8)on lipopolysaccharide(LPS)-induced endotoxic shock(ES)and further investigate its signal transduction pathways involving p38mitogen-activated protein kinase(MAPK)andIкα.METHODS:Eighty-four rats were divided randomly into four groups:LPS(8ng&#183;kg^-1,iv)inducedES;CCK-8(40μg&#183;kg^-1,iv)pretreatment10min before LPS(8mg&#183;kg^-1);CCK-8(40μg&#183;kg^-1,iv)ornormal saline (control)groups.The inflammatory changes of lung and spleen,phagocytic function of alveolar macrophage,quantification of inflammatory cells in bronchoalveolar lavage(BAL)were investigated in rats by using hematoxylin and eosin(HE)staining.phagocytosis of Candida albicans and differential cell counting,Nitric oxide(NO)production in serum,lung and spleen was measured with the griess reaction.The mechanism involving p38mapkandIкB-αsignal pathways was investigated by Western blot.RESULTS:Inflammatory changes of lung and spleen induced by LPS were alleviated by CCk-8,the increase of NOinduced by LPSin serum,lung and spleen was significantly inhibited and the neutrophil infiltration in BALwas significantly reduced by CCK-8,The number of neutrophils was(52&#177;10)&#215;10^6cells&#183;L^-1inCCK-8+LPS(P&lt;0.01).The phagocytic rate of CCK-8 group increased to (62.49&#177;9.94)%,compared with control group(48.16&#177;14.20)%,P&lt;0.05,The phagocytosis rate was(85.14&#177;4.64)%in LPSgroup,which reduced to(59.33&#177;3.14)%inCCK-8|LPSgroup(P&lt;0.01).The results of phagocytosis indexes showed similar changes.CCK-8may play an important role in increasing the expression of p38MAPKand decreasing the degradation of IкB-αin lung and spleen of ES rats. effects,which may be related to activation of p38MAPKand inhibition on the degradation of IкB-α.