地塞米松对哮喘大鼠Th1/Th2失衡及嗜酸性粒细胞凋亡的作用

目的　观察地塞米松对哮喘大鼠Th1/Th2 (T辅助细胞 1/T辅助细胞 2 )平衡、嗜酸性粒细胞 (EOS)凋亡率的影响作用 ,探讨糖皮质激素治疗哮喘的机制。方法　清洁级雄性SD大鼠 30只 ,随机分为 3组 :正常对照组 (C)、哮喘组 (A)、地塞米松治疗组 (T)。卵清白蛋白复制大鼠哮喘模型 ,检测大鼠血、支气管肺泡灌洗液 (BALF)中IL 4、IFN γ水平及气道壁EOS凋亡率。结果　A组大鼠BALF中IFN γ水平明显低于C组 (P <0 0 1) ,血中及BALF中的IL 4水平则明显高于C组 (均为P<0 0 1) ,表现出明显的Th1/Th2失衡。T组大鼠IL 4的表达明显低于A组而IFN γ的表达则明显高于A组 (均为P <0 0 1)。在A组 ,大鼠气道壁EOS的浸润明显增多 ,但凋亡细胞却很少看到 ,EOS凋亡率明显低于C组 (P <0 0 1) ,T组EOS凋亡率则明显高于A组 (P <0 0 1)。结论　纠正哮喘Th1/Th2失衡和促进气道壁EOS凋亡可能是糖皮质激素减轻哮喘气道炎症的重要机制之一。     

哮喘大鼠T辅助细胞功能异常与嗜酸细胞凋亡

为观察哮喘大鼠T辅助细胞 (helperTlymphocyte ,TH) TH1/TH2平衡及嗜酸细胞 (eosinophil,EOS)凋亡率的变化并探讨两者之间的关系。 2 0只清洁级雄性SD大鼠随机分为正常对照组 (C) ,哮喘组 (A) ,每组 10只。卵清白蛋白复制大鼠哮喘模型 ,ELISA法检测血及支气管肺泡灌洗液 (BALF)中IL 4、IFN γ水平 ;TUNEL法检测大鼠气道壁EOS凋亡率。结果显示A组大鼠BALF中IFN γ水平较C组明显降低 (P <0 0 0 1) ;而A组血及BALF中的IL 4水平则均高于C组 (均P <0 0 0 1) ,表现出明显的Th1/Th2失衡。A组大鼠气道壁的EOS浸润明显增多 ,但凋亡细胞却很少看到 ,EOS凋亡率为 (5 2 8± 2 2 1) %明显低于C组 (15 88± 2 39) % (P <0 0 0 1)。以上研究表明哮喘大鼠在气道壁EOS凋亡减少的同时表现为明显的Th1/Th2失衡。     

冬虫夏草菌丝体提取物通过抑制炎性因子及Treg 细胞功能缓解肺纤维化

目的:观察冬虫夏草菌丝体(Hirsutella sinensis mycelium,HSM)提取物对盲肠穿孔结扎(CLP)小鼠的炎症反应和肺纤维化程度的影响。方法:建立CLP 诱导脓毒症5 d 和10 d 小鼠模型,分别分为假术组(sham,n =5)、模型组(CLP,n =11)、治疗组(HSM,n =11)。冬虫夏草菌丝体组在术前2 h 和术后给予HSM 提取物200 mg/ (kg•d)(低于人体用量0.27 g/kg),假术组和模型组给予等量的生理盐水。利用Q-PCR 检测了肺组织中炎性因子TNF鄄琢和IL鄄1茁及纤维化因子TGF-1、TIMP1 和MMP9 的表达;利用流式细胞术分析了小鼠外周血和脾脏中Th1 细胞以及脾脏组织中Treg 细胞的数量;另外,还对肺组织切片进行了HE 染色以及琢鄄平滑肌肌动蛋白( SMA)和纤连蛋白(fibronection)免疫组化染色。结果:模型组外周血和脾脏中Th1 细胞以及脾脏组织中Treg 细胞的数量较假术组显著降低,而HSM 提取物治疗能上调上述细胞的数量。5 d 时,模型组肺组织中IL鄄1茁及纤维化因子TGF-1、MMP9 和TIMP1 表达显著上调,到第10 天时有所降低但仍高于sham 组,而治疗组上述因子表达明显降低;各组肺组织TNF鄄琢表达无显著差异;HE 染色显示模型组肺部炎性样变明显,到第10 天时炎性样变比5 d 时减轻,而治疗组均有改善;免疫组化显示与假术组比,模型组肺内间质 SMA 和fibronection 表达明显增多,而治疗组肺内间质表达低于模型组。结论:HSM 提取物具有抑制炎症、平衡免疫及缓解肺纤维化的功能。     

扩张型心肌病小鼠Th1/Th2细胞亚群及其相关细胞因子的分析

目的:探讨体液免疫在扩张型心肌病发病机制中的重要性。方法:以线粒体腺苷酸转位酶(adeninenucleotidetranslocator,ANT)合成肽免疫液免疫小鼠建立扩张型心肌病动物模型(DCM组) ,运用三色荧光标记流式细胞术检测其脾淋巴细胞中Th细胞亚群分布,ELISA法检测其血清细胞因子IFN γ、IL 4、IL 2、IL 6、TNF α的表达及其抗ANT自身抗体的产生。以不含肽的免疫液免疫小鼠为对照组。结果:DCM组小鼠Th1及Th2细胞亚群较对照组均有增多,以Th2更为显著,且Th1/Th2比值明显低于对照组(P均<0 0 1) ;IL 4、IL 6和TNF α表达明显增高,而IFN γ和IL 2却较对照组明显降低(P均<0 0 1) ;抗ANT自身抗体均为阳性,对照组为阴性。结论:ANT合成肽诱导扩张型心肌病时Th细胞均被激活,Th2细胞介导的体液免疫应答在该病发病机理中起着优势作用。     

寒冷应激对大鼠肾上腺髓质亨廷顿蛋白相关蛋白1表达的影响

目的 探讨亨廷顿蛋白相关蛋白1(HAP1)在大鼠肾上腺髓质的超微结构定位,以及寒冷应激对大鼠肾上腺髓质HAP1表达的影响. 方法 成年雄性Wistar大鼠14只,2只用于免疫电镜研究,12只用于寒冷实验研究.寒冷实验中,将动物随机分为对照组和寒冷组,每组6只,寒冷组动物放置4℃环境下,12h后用免疫组织化学和Western blotting方法 检测大鼠肾上腺髓质HAP1表达的变化. 结果 免疫电镜结果 显示,HAP1免疫反应产物分布在肾上腺髓质细胞分泌颗粒外膜及分泌颗粒间的膜性细胞器上.寒冷组大鼠肾上腺髓质HAP1的表达明显减少,和对照组比较有显著性差异( P <0.01). 结论 HAP1可能与肾上腺髓质细胞内分泌颗粒及位于分泌颗粒内的肾上腺素/去甲肾上腺素的运输和释放有关.     

吗啡依赖大鼠镇痛及生殖功能的改变

目的吗啡依赖大鼠镇痛及生殖功能的改变。方法采用大鼠戒断模型,观察吗啡依赖大鼠下丘脑和血浆茁鄄内啡肽、结状神经节和孤束核P物质(SP)以及血清内分泌激素的变化。结果吗啡依赖大鼠下丘匠脑茁鄄EP的含量均较正常大鼠水平降低,吗啡依赖大鼠结状神经节和孤束核SP的含量升高,吗啡依赖雌性大鼠血清FSH、E2、PRL均低于止常对照组;吗啡依赖大鼠睾丸酮(T)含量显著降低(P<0.01)。结论吗啡依赖大鼠下丘脑—垂体—肾上腺轴可能发生变化。     

腹腔热灌注与顺铂联用增加人卵巢癌细胞系凋亡

目的研究腹腔热灌注(HIPE)和顺铂对人卵巢癌细胞凋亡的影响。方法将人卵巢癌OVCAR-3和A2780细胞各分为对照组、顺铂组、热疗组和热化疗组;显微镜观察卵巢癌细胞形态;AO/GV染色、流式细胞仪检测卵巢癌细胞凋亡细胞比率;荧光定量PCR(q-PCR)检测卵巢癌细胞凋亡相关基因caspase7、caspase9和Bid等。结果 1)顺铂组、热疗组及热化疗组卵巢癌细胞回缩,部分漂浮,其中热化疗组细胞变化最明显;2)顺铂组、热疗组及热化疗组较对照组凋亡细胞增多,其中热化疗组凋亡细胞数量最多(P0.05);3)顺铂组、热疗组、热化疗组较对照组凋亡细胞比率增多,热化疗组凋亡细胞比率最大(P0.05);4)促凋亡相关基因caspase3、caspase6、caspase7、caspase8、caspase9、Bax、Bak和Bid在热化疗组表达明显高于其他各组,凋亡抑制相关基因Bcl-2、Bcl-x L、Mcl-1和c-FLIP表达较其他各组明显下降。结论顺铂和热疗可促进卵巢癌细胞凋亡,且热化疗联合作用效果最明显。     

饲鸽者血清中细胞因子及基因多态性的检测

揭示饲鸽者肺 (PBL )的细胞因子谱及其基因多态性在该病的发病机制中的作用。采取 14 9个饲鸽者的血样 ,根据临床症状以及沉淀抗体出现与否分为四组 :A组 /B组 (抗体阳性、有症状 /无症状 )、C组 /D组 (抗体阴性、有症状 /无症状 )。应用ELISA法检测各组血清细胞因子浓度。应用PCR扩增技术测定TNF α 30 8和IL 10 10 82的基因多态性。与C组 /D组相比 ,A组中Th1细胞因子 (IL 2 )、Th2细胞因子 (IL 4、IL 5、IL 6、IL 10 )和GM CSF浓度有显著的升高。B组中仅Th1细胞因子 (IL 2 )和Th2细胞因子 (IL 4、IL 6、IL 10 )浓度有显著的升高。除个别细胞因子外 ,A组与B组、C组与D组之间细胞因子的表达无显著性差异。各临床组间TNF α 30 8、IL 10 10 82基因型的分布以及不同的基因型间血清TNF α和IL 10的浓度无显著性差异。PBL血浆中IL 2、IL 4、IL 5、IL 6、IL 10和GM CSF的量显著增加 ,细胞因子与抗体相关 ,尤以Th2细胞因子更为显著。在TNF α和IL 10的基因多态性与PBL易感性之间未发现统计学上的关联。     

砷染毒对大鼠睾丸凋亡诱导因子表达及生精细胞凋亡的影响

目的:探讨砷染毒对大鼠睾丸凋亡诱导因子(AIF)表达及生精细胞凋亡的影响。方法:雄性SD大鼠被随机分为对照组和染砷组。采用自由饮用方式进行连续染毒6个月。采用免疫印迹及实时荧光定量PCR检测AIF表达水平;采用TUNEL法观察生精细胞凋亡的情况。结果:免疫印迹及实时荧光定量PCR结果显示,与对照组比较,染砷组大鼠睾丸内AIF蛋白及mRNA表达水平均显著增高。TUNEL法检测结果显示与对照组比较,染砷组生精上皮凋亡细胞平均灰度值显著增高。结论:砷染毒时AIF介导的非caspase依赖性凋亡途径可能参与了大鼠生精细胞凋亡。     

肾上腺素、去甲肾上腺素对小鼠胸腺的影响

目的探讨肾上腺素、去甲肾上腺素对小鼠胸腺的影响。方法取5-6周雄性小鼠,随机分为4组,每组15只,腹腔注射生理盐水（对照组）、肾上腺索和去甲肾上腺素（NE＋E）,分别于5、7、9天后取胸腺,HE染色观察胸腺组织学变化,免疫组织化学法检测胸腺组织中相关凋亡基因Bcl-2和Bax产物的表达,原位末端标记法（TUNEL）计算胸腺组织凋亡细胞数。结果药物处理组的胸腺细胞凋亡均高于对照组（P〈0．05）,而各药物组无显著性差异（P2〉0．05）。结论肾上腺素和去甲肾上腺素可促进小鼠胸腺组织退化,诱导小鼠朐腺细胞凋亡。     

Endotoxin-induced cytokine gene expression in vivo. II. Regulation of tumor necrosis factor and interleukin-1 alpha/beta expression and suppression.

Tumor necrosis factor alpha (TNF alpha) mRNA is present in a preformed intracellular pool in the spleen, liver, and small bowel of naive rats. Endotoxin (Salmonella typhus lipopolysaccharide) injected intravenously induces little or no increase in whole-organ TNF mRNA levels at 15', 30', 1 degree, 2 degrees, or 4 degrees, whereas serum TNF levels are markedly elevated at 1 and 2 hours. Dexamethasone pretreatment of rats suppresses LPS-induced serum TNF concentrations, but does not suppress TNF mRNA levels in the spleen or bowel. Tachyphylaxis experiments demonstrate that a second injection of endotoxin 2 hours after an initial injection fails to induce a second peak of serum TNF, although TNF mRNA levels in the spleen and bowel remain at the levels found in naive rats. Corynebacterium parvum upregulates endotoxin-induced serum TNF release and intravenous injection of IL-1 induces the release of serum TNF but neither alters whole-organ TNF mRNA levels. Interleukin-1 alpha (IL-1 alpha) mRNA was not constitutively detected in whole-organ RNA preparations of the spleen, liver, and small bowel of naive rats. Endotoxin induces IL-1 alpha mRNA most easily appreciated in the spleen beginning at 1 hour, peaking at 2 to 4 hours, and disappearing by 6 hours. Interleukin-1 beta (IL-1 beta) mRNA was not constitutively detected in the organs examined or was present in small amounts. Endotoxin induces IL-1 beta mRNA beginning at 0.5 hours, peaking at 1 hour, and disappearing by 6 hours. Dexamethasone pretreatment prevents the LPS-induced appearance of IL-1 alpha mRNA and suppresses but does not completely inhibit the appearance of IL-1 beta mRNA. C. parvum upregulates endotoxin-induced IL-1 mRNA expression. Intravenous injection of TNF or IL-1 both induce IL-1 mRNA expression. In conclusion, TNF mRNA is constitutively expressed and TNF mRNA levels as analyzed in whole-organ RNA preparations do not change in concert with serum TNF protein levels during conditions of endotoxemia, dexamethasone treatment, tachyphylaxis, priming with C. parvum, or after injection of IL-1. In contrast, IL-1 mRNA expression during endotoxemia, dexamethasone treatment, priming with C. parvum, or after injection of TNF or IL-1 shows clear increases and decreases in whole-organ RNA preparations.     

Endogenous IL-10 regulates sepsis-induced thymic apoptosis and improves survival in septic IL-10 null mice

Recent studies have shown that increased lymphocyte apoptosis contributes to sepsis-induced mortality. Furthermore, studies have demonstrated that IL-10 can suppress lymphocyte apoptosis, in part, by upregulating Bcl-2 expression and interfering with activation induced cell death. We have previously shown that intrathymic delivery of IL-10 with an adenoviral vector in wild-type mice significantly improves outcome to sepsis. Presently, we investigated the role of endogenous IL-10 expression on thymocyte apoptosis and outcome in IL-10 null mice subject to induction of generalized polymicrobial peritonitis via cecal ligation and puncture. Compared to wild-type C57BL/6 mice, IL-10 null mice demonstrated increased mortality and enhanced lymphocyte apoptosis. Intrathymic injection with an adenoviral vector expressing human IL-10 prior to cecal ligation and puncture in IL-10 null mice significantly improved outcome and decreased thymic caspase-3 activity. Furthermore, plasma concentrations of IL-6 were also significantly reduced in IL-10 null mice treated with the IL-10 expressing adenovirus. In contrast, injection of a control adenovirus did not improve outcome in IL-10 null mice, nor was caspase-3 activity reduced. Thus, local thymic expression of IL-10 not only improves outcome but also reduces local tissue apoptosis and caspase-3 activity, and appears to attenuate the systemic proinflammatory cytokine response.     

Protective effect of gliclazide on diabetic peripheral neuropathy through Drp-1 mediated-oxidative stress and apoptosis

Objective: To investigate the protective effect of gliclazide and the role of dynamin-related protein l (Drp-1)-mediated oxidative stress and apoptosis in diabetic peripheral neuropathy (DPN). Methods: Diabetic rats developed through intra-peritoneal injection of streptozotocin were randomly assigned to treatment group receiving gliclazide or non-treatment group without gliclazide treatment. Rats in control group received intra-peritoneal injection of vehicle and no gliclazide treatment. Eight weeks later, the nerve conduction velocity (NCV) of sciatic nerve was measured and the morphological alterations, the malondialdehyde (MDA) level and superoxide-dismutase (SOD) activity, the expressions of Drp-1, caspase-3, Bax and Bcl-2 in sciatic nerve were evaluated. Results: When compared to rats in control group, rats in non-treatment group showed significantly decrease of NCV, obvious demyelinative alteration of sciatic nerve, increased expressions of Drp-1, caspase-3, Bax, Bcl-2 and MDA, and decreased SOD activity. Compared to rats in non-treatment group, rats in treatment group showed significantly increase of NCV, less demyelination of sciatic nerve, decreased expressions of Drp-1, caspase-3, Bax and MDA, and increased activity of SOD. The expression of Bcl-2 was not significantly different between treatment and non-treatment groups. Conclusion: Gliclazide showed protective effect on DPN through modulating Drp-1-mediated oxidative stress and apoptosis.     

玉屏风散对S180荷瘤小鼠Th1／Th2型细胞因子的影响

目的探讨玉屏风散对荷瘤小鼠Th1／Th2型细胞因子产生的影响。方法采用体外培养S180肉瘤细胞，接种C57BL／6纯系小鼠，建立荷瘤小鼠模型，设正常对照、荷瘤对照及玉屏风散给药组，检测各组脾脏T淋巴细胞增殖能力及Th1（IL-2、IFN-γ）和Th2（IL-4、IL-10）细胞因子产生水平。结果荷瘤组T细胞增殖能力明显下降，Th2型细胞因子IL-10的产生明显增加，与正常对照组比较均有统计学意义（P〈0．01），而IL-4的含量略有增加，但无统计学意义。Th1型细胞因子IL-2及IFN-γ的产生明显减少，与正常对照组比较有统计学意义（P〈0．01，P〈0．05）。玉屏风散给药对T细胞增殖能力及细胞因子的产生有较为明显的调节作用，与荷瘤组比较T细胞增殖能力及IL-2、IFN-γ的产生明显增加（P〈0．01），Th2型细胞因子IL-10的血清含量下降（P〈0．01）．IL-4的含量略有下降，但与荷瘤对照组比较无统计学意义。结论玉屏风散可有效调节荷瘤小鼠的免疫功能，促进荷瘤鼠Th1型细胞因子的产生，有效纠正荷瘤导致Th1／Th2的失衡，增强机体的抗肿瘤免疫功能。     

热致死发酵乳杆菌对牛乳β-乳球蛋白过敏小鼠的免疫调节作用

目的:观察热致死的发酵乳杆菌对牛乳β-乳球蛋白(BLG)致敏小鼠Th1/Th2细胞平衡、血清抗体水平及T细胞亚群数量的影响,探讨其缓解过敏反应的作用。方法:用牛乳BLG和弗氏佐剂的混合液腹腔注射诱发BALB/c小鼠致敏,建立动物过敏模型。将实验动物随机分为空白组、致敏组和不同剂量的热致死发酵乳杆菌组。采用ELISA法测定各组小鼠血清总IgE、BLG特异性IgE和总IgG含量。体外分离培养各组小鼠脾细胞,采用ELISA法检测细胞上清液中Th1型细胞因子(IL-12、IFN-γ)和Th2型细胞因子(IL-4)水平,采用流式细胞术检测脾淋巴细胞中CD3+、CD4+和CD8+T百分含量。结果:发酵乳杆菌组小鼠脾细胞培养上清液中IFN-γ/IL-4比值为13.53,显著高于致敏组的3.34(P<0.05);血清总IgE、BLG特异性IgE和总IgG水平显著降低(P<0.05);脾细胞中CD3+和CD4+T细胞比例升高,CD4+/CD8+比值趋近正常组。特别是高剂量的热致死发酵乳杆菌组小鼠脾细胞培养上清液中抑制IL-4分泌的效果显著优于致敏组(P>0.05),且该组小鼠血清的抗体水平和CD4+/CD8+比值与空白组相比无差异(P>0.05)。结论:热致死的发酵乳杆菌干预可改善小鼠的BLG过敏症状,其作用可能与促进Th1占优势的Th1/Th2细胞平衡,阻断IgE、IgG分泌及平衡T细胞亚群数量相关。     

IL-12 prevents neonatal induction of transplantation tolerance in mice

We investigated the effect of IL-12 on the induction of transplantation tolerance by neonatal injection of allogenic cells. We first observed that injection of newborn BALB/c mice with IL-12 and (A/J × BALB/c) F1 spleen cells prevented the Th2 alloimmune response induced by neonatal inoculation of F1 cells alone and allowed the differentiation of T cells secreting high amounts of IL-2 and IFN-γ in mixed lymphocyte cultures with donor-type stimulators. Furthermore, IL-12 administration resulted in the emergence of anti-donor cytotoxic T lymphocyte responses although at lower levels than in control uninjected mice. In parallel, we found that mice injected at birth with IL-12 and F1 cells did not develop chimerism and were able to reject a donor-type skin graft as efficiently as control mice. We conclude that IL-12 inhibits the Th2 polarization of the newborn response to alloantigens and prevents thereby the establishment of transplantation tolerance.     

健脾补肾药对脾虚大鼠细胞因子水平的影响

目的 :观察健脾补肾方药对实验性脾虚证大鼠细胞因子的影响 ,探讨脾虚证与细胞因子的关系及脏腑相关的意义。方法 :选用SD雄性大鼠 ,随机分为 :正常对照组 ,脾虚模型组 ,健脾补肾方高、低剂量组 ,通过大黄复制脾虚证动物模型 ,并用健脾补肾方药进行防治。采用放射免疫分析观察各组动物血清肿瘤坏死因子(TNF)、白细胞介素 - 6 (IL - 6 )、白细胞介素 - 2 (IL - 2 )水平的变化。结果 :脾虚模型组大鼠血清TNF、IL - 6、IL - 2含量均比正常对照组显著降低 (p <0 0 1) ,而健脾补肾方药能明显升高TNF、IL - 6、IL - 2含量 ,使体重增加 ,脾脏和胸腺组织的重量增加。结论 :脾虚证的发生与细胞因子网络调节系统的失衡有关 ,而健脾补肾中药对实验性脾虚证有较好的防治作用 ,脾肾相关理论对实践有指导意义。     

白介素10对脑缺血大鼠神经细胞凋亡的作用研究

目的:探讨白介素10(IL-10)对大鼠脑缺血梗死灶周围神经细胞凋亡的作用。方法:成年雄性Sprague-Darley大鼠36只,随机分为假手术组(Sham组)、局灶性脑缺血组(MCAO组)和脑缺血 IL-10干预组(IL-10组),术后24h断头取脑,TUNEL法(Terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling)测定梗死灶周围凋亡神经细胞的数目,免疫组化和RT-PCR法检测促凋亡基因Fas、FasL和caspase-3的表达。结果:脑缺血诱导神经细胞凋亡显著增多(P<0.05),Fas,FasL和caspase-3表达显著上调(P<0.05);IL-10干预可显著减少脑缺血神经细胞凋亡(P<0.05),并抑制FasL和caspase-3的表达(P<0.05),而对Fas的表达无明显作用(P>0.05)。结论:IL-10可抑制大鼠脑缺血梗死灶周围神经细胞凋亡,其机制可能与抑制促凋亡基因FasL和caspase-3的表达有关。     

丝胶对Ⅱ型糖尿病模型大鼠脾干扰素-γ、肿瘤坏死因子-α、白介素-4、白介素-10水平的影响

目的:观察丝胶对Ⅱ型糖尿病模型大鼠脾干扰素-γ(IFN-γ)、肿瘤坏死因子-α(TNF-α)、白介素(IL)-4、IL-10水平的影响,以探讨其对免疫功能调节的可能机制。方法:小剂量链脲佐菌素连续腹腔注射建立Ⅱ型糖尿病大鼠模型。SD大鼠随机分为正常对照组、模型组、丝胶治疗组和二甲双胍组。丝胶治疗组和二甲双胍组分别给予丝胶和二甲双胍灌胃治疗35 d。4组均采用葡萄糖氧化酶法检测Ⅱ型糖尿病模型大鼠血糖,免疫印迹和RT-PCR法分别检测脾IFN-γ、TNF-α、IL-4、IL-10蛋白及mRNA的表达,并比较。结果:与正常对照组大鼠相比,模型组大鼠血糖、脾IFN-γ和TNF-α的水平均明显升高,脾IL-4和IL-10的水平均明显降低。与模型组大鼠相比,丝胶治疗组和二甲双胍组大鼠血糖、脾IFN-γ和TNF-α的水平均明显降低,脾IL-4和IL-10的水平均明显升高。结论:丝胶可通过下调脾IFN-γ和TNF-α的表达,上调IL-4和IL-10的表达,发挥免疫调节作用。     

Norepinephrine and vasopressin counteract anti-inflammatory effects of isoflurane in endotoxemic rats

Volatile anesthetics such as isoflurane have been shown to offer anti-inflammatory effects during experimental endotoxemia whereas the alpha-adrenergic vasopressor norepinephrine exhibits proinflammatory properties on systemic cytokine release under the same conditions. However, during major surgery and in patients with systemic inflammatory response syndrome or sepsis both agents are frequently administered concurrently. We therefore aimed to investigate the influence of preexisting i.v. administration of noradrenaline or vasopressin on the anti-inflammatory effects of isoflurane during experimental endotoxemia. Anesthetized, ventilated Sprague-Dawley rats (n=7 per group) were randomly treated. In the LPS-only group, animals received lipopolysaccharide (LPS, 5 mg/kg, i.v.) with no further specific treatment. In the LPS-isoflurane group, isoflurane inhalation at 1 MAC was initiated simultaneously with induction of endotoxemia (LPS 5 mg/kg, i.v.). Animals in the LPS-isoflurane-norepinephrine group received norepinephrine infusion at 50 microg/kg/h 10 min prior to injection of LPS and inhalation of isoflurane. In the LPS-isoflurane-vasopressin group, vasopressin was administered at 0.5 IE/kg/h 10 min prior to LPS and isoflurane. In the LPS-norepinephrine and the LPS-vasopressin groups the infusion of each vasopressor was started prior to LPS injection without any application of isoflurane. A Sham group served as the control. After 4 h of endotoxemia, plasma levels of TNFalpha, IL-1beta and IL-10 were measured. Alveolar macrophages (AM) were cultured ex vivo for nitrite assay. Induction of endotoxemia resulted in a significant rise in measured plasma cytokines and nitrite production from cultured AM. Inhalation of isoflurane significantly attenuated plasma levels of TNFalpha (-65%) and IL-1beta (-53%) compared to the LPS-only group whereas it had no effect on nitrite production from cultured AM. Preexisting infusions of norepinephrine or vasopressin abolished the anti-inflammatory effects of isoflurane. The data demonstrate that the administration of norepinephrine or vasopressin both counteracted the anti-inflammatory effects of inhaled isoflurane on proinflammatory cytokine release during experimental endotoxemia in rats.