盐酸戊乙奎醚对内毒素性急性肺损伤大鼠肺组织Toll样受体4mRNA和Toll样受体2mRNA表达的影响

Objective To investigate the effect of penehyclidine (PHCD) on Toll-like receptor 4 (TLR4)mRNA and Toll-like receptor 2 (TLR2) mRNA expression in the lung tissue in rats with acute lung injury induced by lipopolysaccharide (LPS) .Methods Sixty healthy SD rats of both sexes weighing 200-220 g were randomly divided into 5 groups ( n = 12 each) :control group (group C) , LPS group and P1-3 groups. Acute lung injury was induced by intraperitoneal (IP) LPS 8 mg/kg in LPS and P1-3 groups. PHCD 0.3, 1.0 and 3.0 mg/kg were given IP after LPS administration in P1-3 groups. The animals were anesthetized at 6 h after IP LPS. Blood samples were collected for determination of serum TNF-α and IL-6 concentrations ( by ELISA) and then sacrificed, the lungs were immediately removed for determination of TLR4 mRNA and TLR2 mRNA expression (by RT-PCR), and microscopic examination. Results LPS significantly increased TLR4 mRNA and TLR2 mRNA expression in the lung tissue and serum TNF-α and IL-6 concentrations. PHCD 1.0 or 3.0 mg/kg significantly inhibited LPS-induced increase in TLR4 mRNA and TLR2 mRNA expression in the lung tissue and serum TNF-α and ILr6 concentrations.The lung histopathologic damage was significantly ameliorated in P2 and P3 groups as compared with group LPS.Conclusion PHCD can protect the lungs against LPS-induced acute lung injury through inhibiting TLR4 mRNA and TLR2 mRNA expression in the lung tissue and reducing the inflammatory response.     

盐酸戊乙奎醚对内毒素性急性肺损伤大鼠肺组织Toll样受体4mRNA和Toll样受体2mRNA表达的影响

目的 探讨盐酸戊乙奎醚对内毒索性急性肺损伤大鼠肺组织Toll样受体4(TLR4)mRNA和Toll样受体2(TLR2)mRNA表达的影响.方法 健康SD大鼠60只,雌雄不拘,体重200～220g,采用随机数字表法,将大鼠随机分为5组(n=12),对照组(C组)、LPS组和低、中、高剂量盐酸戊乙奎醚组(P1组～P3组).C组腹腔注射生理盐水2ml;LPS组腹腔注射LPS 8mg/kg;P1组～P3组分别腹腔注射LPS 8 mg/kg和盐酸戊乙奎醚0.3、1.0和3.0 mg/kg.给药结束后6 h时开胸,心室取血,并取肺组织,采用ELISA法测定血清TNF-α和Ib-6的浓度,RT-PCR法测定肺组织TLR4 mRNA和TLR2 mRNA 的表达水平,并观察肺组织病理学结果.结果 与C组比较,LPS组、P1组～P3组血清TNF-α、IL-6浓度和肺组织TLR4 mRNA、TLR2 mRNA表达均升高(P<0.05);与LPS组比较,P2组和P3组血清TNF-α、IL-6浓度和肺组织TLR4 mRNA、TLR2 mRNA表达均降低(P<0.05),P1组上述指标差异无统计学意义(P>0.05);与P1组比较,P2组和P1组血清TNF-α、IL-6浓度和肺组织TLR4 mRNA、TLR2 mRNA表达均降低(P<0.05);P2组和P3组血清TNF-α、IL-6浓度和肺组织TLR4 mRNA、TLR2 mRNA表达比较差异无统计学意义(P>0.05).P2组和P3组肺组织病理学损伤程度明显轻于LPS组.结论 盐酸戊乙奎醚可通过下调肺组织TLR4 mRNA和耵JR2 mRNA的表达,降低炎性反应,从而减轻大鼠内毒素性急性肺损伤.

Abstract：

Objective To investigate the effect of penehyclidine (PHCD) on Toll-like receptor 4 (TLR4)mRNA and Toll-like receptor 2 (TLR2) mRNA expression in the lung tissue in rats with acute lung injury induced by lipopolysaccharide (LPS) .Methods Sixty healthy SD rats of both sexes weighing 200-220 g were randomly divided into 5 groups ( n = 12 each) :control group (group C) , LPS group and P1-3 groups. Acute lung injury was induced by intraperitoneal (IP) LPS 8 mg/kg in LPS and P1-3 groups. PHCD 0.3, 1.0 and 3.0 mg/kg were given IP after LPS administration in P1-3 groups. The animals were anesthetized at 6 h after IP LPS. Blood samples were collected for determination of serum TNF-α and IL-6 concentrations ( by ELISA) and then sacrificed, the lungs were immediately removed for determination of TLR4 mRNA and TLR2 mRNA expression (by RT-PCR), and microscopic examination. Results LPS significantly increased TLR4 mRNA and TLR2 mRNA expression in the lung tissue and serum TNF-α and IL-6 concentrations. PHCD 1.0 or 3.0 mg/kg significantly inhibited LPS-induced increase in TLR4 mRNA and TLR2 mRNA expression in the lung tissue and serum TNF-α and ILr6 concentrations.The lung histopathologic damage was significantly ameliorated in P2 and P3 groups as compared with group LPS.Conclusion PHCD can protect the lungs against LPS-induced acute lung injury through inhibiting TLR4 mRNA and TLR2 mRNA expression in the lung tissue and reducing the inflammatory response.     

盐酸戊乙奎醚预先给药对新生大鼠内毒素性急性肺损伤时NF-κB活性的影响

Objective To investigate the effects of penehyclidine (PHCD) pretreatment on nuclear factor kappa B ( NF-kB ) activity during lipopolysaccharide ( LPS )-induced acute lung injury ( ALl ) in neonate rats.Methods Thirty 7-day old Wistar rats of both sexes weighing 18-21 g were randomly divided into 3 groups ( n =10 each): group Ⅰ control (group C); group Ⅱ LPS; group Ⅲ PHCD. Group Ⅱ and Ⅲ received intraperitoneal ( group IP) LPS 3 mg/kg. In group Ⅲ PHCD 5 mg/kg was administered IP at 30 min before LPS respectively. The animals were killed at 4 h after LPS administration. The lungs were immediately removed. The W/D lung weight ratio was measured. The TNF-α, IL-1 βand IL-10 content in the lung were detected by ELISA and expression of NF-kB p65 was detected by immuno-histochemical staining.Results LPS significantly increased W/D lung weight ratio, TNF-α, IL-1 β, IL-10 content and NF-kB p65 expression in the lung as compared with control group. PHCD administered before LPS significantly attenuated the LPS-induced changes. Electron microscopy showed that PHCD before LPS significandy ameliorated the LPS-induced histological damages. Conclusion Pretreatment with PHCD can attenuate LPS-induced acute lung injury though inhibition of NF-kB activation and inflammatory response of lung tissue in neonate rats.     

盐酸戊乙奎醚预先给药对新生大鼠内毒素性急性肺损伤时NF-κB活性的影响

Objective To investigate the effects of penehyclidine (PHCD) pretreatment on nuclear factor kappa B ( NF-kB ) activity during lipopolysaccharide ( LPS )-induced acute lung injury ( ALl ) in neonate rats.Methods Thirty 7-day old Wistar rats of both sexes weighing 18-21 g were randomly divided into 3 groups ( n =10 each): group Ⅰ control (group C); group Ⅱ LPS; group Ⅲ PHCD. Group Ⅱ and Ⅲ received intraperitoneal ( group IP) LPS 3 mg/kg. In group Ⅲ PHCD 5 mg/kg was administered IP at 30 min before LPS respectively. The animals were killed at 4 h after LPS administration. The lungs were immediately removed. The W/D lung weight ratio was measured. The TNF-α, IL-1 βand IL-10 content in the lung were detected by ELISA and expression of NF-kB p65 was detected by immuno-histochemical staining.Results LPS significantly increased W/D lung weight ratio, TNF-α, IL-1 β, IL-10 content and NF-kB p65 expression in the lung as compared with control group. PHCD administered before LPS significantly attenuated the LPS-induced changes. Electron microscopy showed that PHCD before LPS significandy ameliorated the LPS-induced histological damages. Conclusion Pretreatment with PHCD can attenuate LPS-induced acute lung injury though inhibition of NF-kB activation and inflammatory response of lung tissue in neonate rats.     

盐酸戊乙奎醚对大鼠胸部撞击致急性肺损伤及肺组织Toll样受体4表达的影响

目的 探讨盐酸戊乙奎醚对大鼠胸部撞击致急性肺损伤及肺组织Toll样受体4(TLR4)表达的影响.方法 健康雄性SD大鼠96只,体重250～300 g,采用随机数字表法,将大鼠随机分为3组(n=32):对照组(C组)只麻醉,不制备模型;肺损伤组(ALI组);盐酸戊乙奎醚组(PHcD组)模型制备后即刻,腹腔注射盐酸戊乙奎醚2 mg/kg.砝码(300g)于95 cm高处自由落体撞击大鼠心前区以制备急性肺损伤模型.于模型制备后2、8、12和24h时取8只大鼠,取动脉血样,测定血清TNF-α浓度.于模型制备后8 h取8只大鼠,取动脉血样,行动脉血气分析,随后处死大鼠,取肺组织观察病理学结果,测定干/湿重比(W/D比)、髓过氧化物酶(MPO)活性和TLR4表达水平.结果 与c组比较,ALI组和PHCD组pH值和PaO2下降,PaCO2、乳酸浓度、肺组织MPO活性、W/D比及TLR4表达和血清TNF-α浓度升高(P＜0.01);与ALI组比较,PHcD组pH值和PaO2升高,PaCO2、乳酸浓度、肺组织MPO活性、W/D比及TLR4表达和血清TNF-α浓度降低(P＜0.05).PHcD组肺组织病理性损伤较ALI组减轻.结论 盐酸戊乙奎醚可减轻大鼠胸部撞击诱发的急性肺损伤,其机制与下调肺组织TLR4表达,降低炎性反应有关.

Abstract：

Objective To investigate the effects of penehyclidine hydrochloride (PHCD) on acute lung injury (ALI) induced by blunt chest trauma and Toll-like receptor 4 (TLR4) expression in the lung tissues in rats.Methods Ninety-six male SD rats weighing 250-300 g were randomly divided into 3 groups ( n = 32 each):control group (group C), ALI group and PHCD group. ALI was induced by dropping a 300 g weight onto a precordial protective shield to direct the impact force away from the heart and toward the lungs in anesthetized rats according to the method described by Raghavendran et al. PHCD 2 mg/kg was injected intraperitoneally immediately after ALI was induced in group PHCD. Eight rats were selected at 2, 8, 12 and 24 h after ALI was induced, and arterial blood samples were collected for determination of the serum TNF-α concentration. Eight rats were selected at 8 h after ALI was induced, arterial blood samples collected for blood gas analysis and then the rats sacrificed. The lungs were immediately removed for determination of W/D lung weight ratio, myeloperoxidase (MPO) activity and TLR4 expression, and microscopic examination. Results The pH value and PaO2 were significantly lower, and the PaCO2, lactic acid level, MPO activity, W/D ratio, TLR4 expression and serum TNF-α concentration higher in groups ALI and PHCD than in group C (P ＜ 0.01 ). The pH value and PaO2 were significantly higher, and the PaCO2, lactic acid level, MPO activity, W/D ratio, TLR4 expression and serum TNF-α concentration lower in group PHCD than in group ALI ( P ＜ 0.05). The lung histopathologic damage was significantly ameliorated in PHCD group as compared with ALI group. Conclusion PHCD can protect the lungs against blunt chest trauma-induced ALI, and the down-regulation of TLR4 expression in lung tissues and reduction of inflammatory response are involved in the mechanism.     

骨髓间充质干细胞对急性出血坏死性胰腺炎大鼠肺组织Toll样受体2/4mRNA表达的影响及意义

目的 研究骨髓间充质干细胞(BMSCs)对急性出血坏死性胰腺炎(AHNP)大鼠肺组织T0ll样受体(TLR)2/4表达的影响并初步探讨其机制.方法 采用逆行胰胆管牛磺胆酸钠注射制造AHNP大鼠模型,动物分为假手术组、胰腺炎组和BMSCs治疗组;流式细胞仪检测BMSCs表面标记阳性细胞率;RT-PCR方法检测肺组织TLR2/4mRNA表达变化;同时观察肺组织形态学改变,进行肺湿/干重比(W/D)测定.结果 与假手术组比较,胰腺炎组大鼠从3h时肺组织TLR2/4mRNA表达开始增高,在12 h时肺组织TLR2/4mRNA表达达到峰值;同时肺损伤加重,肺组织TNF-α浓度升高(P＜0.05).给予BMSCs治疗后,TLR2/4mRNA表达降低,肺损伤程度减轻,肺组织TNF-α浓度降低(P＜0.05).结论 急性出血坏死性胰腺炎时,组织内TLR2和TLR4mRNA表达上调,肺组织损伤加重.BMSCs可以明显抑制AHNP肺组织TLR2/4mRNA的表达,降低肺组织TNF-α浓度,从而减轻肺损伤.

Abstract：

Objective To investigate the effect of bone mesenchymal stem cells on Toll-like receptors (TLR) 2/4 expression in the lungs of rats with acute hemorrhagic necrotizing pancreatitis (AHNP). Methods Seventy SD male rats were randomly divided into sham-operation group (n=10), AHNP group(n=30) and MSCs-treated group(n=30). Masc rate of BMSCs with surface mark were measured by flow cytometer. TLR2/4mRNA expression in the the lung were measured by RT-PCR, and The ratio of Wet/dry and lung histological changs were observed. Results TLR2/4 mRNA could be detected in the lungs with low values in sham-operation group, markedly increased in 3 h, and peaked in 12 h in AHNP group (P＜0.05). Lung injuries were aggravated and the levels of TNF-α in the lung were increased (P＜0. 05) . Treatment with MSCs could effectively inhibit TLR2/4 mRNA expression and relieve lung injuries. The levels of TNF-α in the lung were decreased (P＜0.05). Conclusions The expression of TLR2/4 mRNA is increased in the lungs in AHNP and the lung injuries are aggravated. MSCs could markedly inhibit TLR2/4 mRNA expression in the lungs in AHNP, which would lead to relief of lung injury.     

Effect of propofoi on LPS-induced TLR4 expression in rat alveolar type Ⅱ epithelial cells

Objective To investigate the effect of propofol on LPS-induced TLR4 expression in rat alveolar type Ⅱ epithelial cells. Methods The primarily cultured alveolar type Ⅱ epithelial cells isolated from male rats were randomly assigned to one of 5 groups: group Ⅰ cells were incubated for 3 h without any additive (control) ; group Ⅱ cells were incubated with LPS 1 μg/ml for 3 h (LPS) ; group Ⅲ , Ⅳ , Ⅴ cells were incubated with LPS 1 μg/ml + propofol 25, 50 and 100 μmol/L respectively for 3 b (P1-3). TLR4 mRNA and TLR4 protein expression was detected by real time PCR and Western blot. TNF-α release amount was measured using ELISA. Results LPS significantly' increased TLR4 mRNA and protein expression in alveolar type Ⅱ epithelial cells as well as TNF-α release amount. Propefol at 50 and 100 μmol/L significantly inhibited LPS-imluced increase in TLR4 mRNA and protein expression and TNF-α release amount. Conclusion Propofol can dose-dependently inhibit LPS-induced inflammation in alveolar type Ⅱ epithelial ceils, through down-regnlation of TLR4 gene and protein expression.     

右美托咪啶对脂多糖诱导大鼠外周血单核细胞Toll样受体4mRNA表达的影响

目的 探讨右美托咪啶对脂多糖(LPS)诱导大鼠外周血单核细胞Toll样受体4(TLR4)mRNA表达的影响.方法 健康雄性Wistar大鼠40只,取外周血分离培养单核细胞,采用随机数字表法,将其随机分为5组(n=8),A组:阴性对照;B组:单核细胞中加入LPS(终浓度为1μg/ml);C组:单核细胞中加入LPS(终浓度为1μg/ml)+右美托咪啶(终浓度为0.5 ng/ml);D组:单核细胞中加入LPS(终浓度为1μg/ml)+右美托咪啶(终浓度为5.0 ng/ml);E组:单核细胞中加入LPS(终浓度为1μg/ml)+右美托咪啶(终浓度为50.0 ng/ml).孵育24 h后,收集上清液,采用ELISA法测定TNF-α、IL-1β和IL-6的浓度,采用RT-PCR法测定TLR4 mRNA的表达.结果 与A组比较,B组TNF-α、IL-1p、IL-6的浓度升高,TLR4 mRNA表达上调(P＜0.01);与B组比较,C组、D组和E组TNF-α、IL-1β、IL-6的浓度降低,TLR4 mRNA表达下调(P＜0.05或0.01);与C组比较,D组和E组TNF-α、IL-1β、IL-6的浓度降低(P＜0.01),TLR4 mRNA表达差异无统计学意义(P＞0.05);D组和E组各指标比较差异无统计学意义(P＞0.05).结论 右美托咪啶可通过下调TLR4 mRNA表达,抑制TLR4的合成,从而抑制LPS诱导大鼠外周血单核细胞TNF-α、IL-1β和IL-6的生成与释放.

Abstract：

Objective To investigate the effects of different concentrations of dexmedetomidine on the expression of Toll-like receptor 4 (TLR4) mRNA in rat peripheral blood monocytes exposed to lipopolysaccharide ( LPS ). Methods Peripheral blood monocytes isolated from male Wistar rats were seeded in 24-well plate in RPMI 1640 liquid culture medium in CO2 incubator at 37 ℃ and 5% CO2 for 2 h, and were randomly divided into 5 groups ( n = 8 each): group A negative control; group B was exposed to LPS 1 μg/ml and C, D and E groups were exposed to LPS 1 μg/ml + dexmetomidine 0.5, 5.0 and 50.0 ng/ml respectively. The monocytes were then incubated for 24 h. The concentrations of TNF-α, IL-1β and IL-6 in the supernatant of the cultured monocytes were detected by ELISA. The expression of TLR4 mRNA in the monocytes was detected by RT-PCR.Results Exposure to LPS significantly increased the expression of TLR4 mRNA and the concentrations of TNF-α, IL-1β and IL -6 in group B as compared with group A ( P ＜ 0.01 ). Dexmedetomidine attenuated the LPS-induced increase in the expression of TLR 4 mRNA and the concentrations of TNF-α, IL-1β and IL-6 in a dose-dependent manner ( P ＜0.05or 0.01 ). Conclusion Dexmedetomidine can inhibit the synthesis of TLR4 and inhibit the secretion and dilivery of TNF-α, IL-1β and IL-6 by down-regulating the gene expression of TLR4 in rat peripheral blood monocytes exposed to LPS.     

c-Jun氨基末端激酶在大鼠内毒素性急性肺损伤中的作用

Objective To evaluate the role of c-Jun N-terminal kinase (JNK) in lipopolysaccharide (LPS)-induced acute lung injury ( ALI) in rats.Methods Eighty male SD rats weighing 250-300 g were randomly divided into 4 groups ( n = 20 each) : control group (group C) ; ALI group; LPS + SP600125 (JNK inhibitor)group (group S) and LPS+ DMSO (the solvent) group (group DMSO) . ALI was induced by intravenous LPS 5mg/kg. In S and DMSO groups, SP600125 30 mg/kg and DMSO 0.2 ml were injected intravenously after LPS administration respectively. Ten animals were sacrificed by exsanguinafions at 4 h after LPS administration in each group. The broncho-alveolar lavage fluid (BALF) was colleted. The TNF-α and IL-1β concentrations in BALF were measured. The lungs were removed for microscopic examination and determination of W/D lung weight ratio. The other 10 animals in each group were observed for 48 h survival rate. Results Intravenous LPS significantly increased TNF-α and IL-1β concentrations in BALF and W/D lung weight ratio, decreased 48 h survival rate and induced histologic damage. Intravenous SP600125 30 mg/kg significantly attenuated the above-mentioned LPS-induced changes. Conclusion Activation of JNK is involved in the development of endotoxin-induced ALI in rats.     

c-Jun氨基末端激酶在大鼠内毒素性急性肺损伤中的作用

Objective To evaluate the role of c-Jun N-terminal kinase (JNK) in lipopolysaccharide (LPS)-induced acute lung injury ( ALI) in rats.Methods Eighty male SD rats weighing 250-300 g were randomly divided into 4 groups ( n = 20 each) : control group (group C) ; ALI group; LPS + SP600125 (JNK inhibitor)group (group S) and LPS+ DMSO (the solvent) group (group DMSO) . ALI was induced by intravenous LPS 5mg/kg. In S and DMSO groups, SP600125 30 mg/kg and DMSO 0.2 ml were injected intravenously after LPS administration respectively. Ten animals were sacrificed by exsanguinafions at 4 h after LPS administration in each group. The broncho-alveolar lavage fluid (BALF) was colleted. The TNF-α and IL-1β concentrations in BALF were measured. The lungs were removed for microscopic examination and determination of W/D lung weight ratio. The other 10 animals in each group were observed for 48 h survival rate. Results Intravenous LPS significantly increased TNF-α and IL-1β concentrations in BALF and W/D lung weight ratio, decreased 48 h survival rate and induced histologic damage. Intravenous SP600125 30 mg/kg significantly attenuated the above-mentioned LPS-induced changes. Conclusion Activation of JNK is involved in the development of endotoxin-induced ALI in rats.     

门静脉高压症脾功能亢进脾巨噬细胞Toll样受体2、4 mRNA表达变化的研究

目的 检测门静脉高压症(PH)脾亢脾和正常脾巨噬细胞(Mφ)中Toll样受体2、4(TLR2、4) mRNA的表达差异,为进一步深入探讨Toll样受体在PH脾亢发生中的作用奠定基础.方法 选取门静脉高压症脾亢患者(均为慢性乙型肝炎患者)的手术切除脾脏(12例)为实验组,外伤性脾破裂患者的手术切除脾脏(4例)为正常对照组.贴壁培养法分离纯化脾脏组织Mφ,荧光定量PCR法对Mφ表面Toll样受体2、4 mRNA的表达进行检测,并将两组结果进行统计学分析比较.结果 与正常脾脏相比,PH脾亢脾Mφ TLR2、4 mRNA的表达水平明显增强(TLR2:2.29±0.55 vs 1.06±0.53,P <0.05;TLR4:2.32±0.41 vs 1.01±0.14,P <0.01).结论 PH脾亢脾Mφ TLR2、4的mRNA表达水平明显升高,与蛋白水平免疫组化的结果一致,进一步支持了"内毒素血症→脾脏Mφ Toll样受体活化→Mφ吞噬破坏血细胞增多"是PH脾亢发生可能机制的观点.     

脓毒症大鼠心肌Toll样受体4和髓样分化蛋白-2基因表达的变化和意义

目的探讨脓毒症大鼠心肌组织内毒素信号转导复合受体．Toll样受体4（TLR4）／髓样分化蛋白．2（MD2）基因表达的变化情况。研究其与心肌组织肿瘤坏死因子-α（TNF-α）基因表达的关系。方法采用腹腔注射5mg／kg体重内毒素（LPS）制作大鼠脓毒症模型。动物分为正常对照组（10只），内毒素注射后1、2、6h组（各10只），利用逆转录-聚合酶链反应（RT-PCR）方法检测心肌组织TLR4／MD2以及TNF-α的基因表达。结果LPS注射后1h，TLR4／MD-2及TNF-α基因表达开始升高，2h达高峰，6h逐渐下降，各时间点的表达均显著高于对照组（P〈0．01）。相关分析表明，心肌TUM／MD2基因表达分别与TNF-α基因表达呈显著正相关（P〈0．05）。结论LPS可上调心肌组织TLR4／MD-2基因表达并诱导早期炎症细胞因子TNF-α基因表达。TLR4识别LPS信号是以TLR4／MD-2复合受体的形式完成的。而且在识别过程中，MD-2是TLR4必需的作用分子。     

Toll样受体与消化系统肿瘤的研究进展

消化系统恶性肿瘤是最常见的一类恶性肿瘤,严重威胁人类健康,然而目前对其病因及发病机制尚不明确.Toll样受体(Toll-like receptors,TLRs)是一种跨膜受体,在固有免疫中起着重要作用,新近发现TLRs与炎性介质、自身免疫性疾病、肿瘤等有密切联系.已有研究表明TLRs广泛参与消化系统恶性肿瘤的发生发展、免疫逃逸,并在免疫治疗中发挥作用,对TLRs的深入研究可揭示TLRs在常见消化系统恶性肿瘤发生发展中的作用,并可能寻找到治疗肿瘤的新靶点.本文将对TLRs与常见消化系统恶性肿瘤的关系作一综述.     

Toll样受体4的基因多态性与脓毒症

脓毒症是指机体感染微生物后发生的全身炎性反应综合征.在该疾病发生发展中是基因多态性影响着机体对该综合征的遗传易感性.其中Toll样受体4(toll-like receptor4,TLR4)作为识别病原微生物的主要受体之一,在自身免疫中起着重要的作用.已有研究表明TLR4的基因多态性与脓毒症的遗传易感性密切相关,其中TLR4基因的Asp299Gly和Thr399Ile位点的突变与脓毒症的发生发展及预后有关.现就TLR4的功能、信号转导通路及其基因多态性与脓毒症易感性的相关关系作一综述.     

右美托咪啶对老年患者术后认知功能和围术期单核细胞Toll样受体2和Toll样受体4表达的影响

目的 探讨右美托咪啶对老年患者术后认知功能和围术期单核细胞Toll样受体2(TLR2)和TLR4表达的影响.方法 择期手术治疗的腰椎间盘突出症和腰椎骨折患者45例,年龄≥65岁,体重53～72 kg,ASA分级Ⅰ或Ⅱ级,采用随机数字表法,将其随机分为3组(n=15):对照组(Ⅰ组)和不同剂量右美托咪啶组(Ⅱ组和Ⅲ组).麻醉诱导结束后静脉输注右美托咪啶负荷剂量1.0μg/kg,输注时间15 min,然后以0.5μg/·kg-1·h-1(Ⅱ组)或1.0 μg·Jg-1·h-1(Ⅲ组)的速率静脉输注至术毕,Ⅰ组给予等容量生理盐水.于麻醉诱导前(T1)、手术开始1.5 h(T2)、术毕(T3)和术后24 h(T4)时取静脉血样,检测外周血单核细胞TLR2及TLR4的表达.分别于术前1d和术后7d时采用简易精神状态量表评分和韦氏成人记忆量表及智力量表评价认知功能,记录术后认知功能障碍的发生情况.结果 与Ⅰ组比较,Ⅱ组和Ⅲ组术后认知功能障碍发生率降低,T2～T4时单核细胞TLR2和TLR4表达下调(P＜0.05);与Ⅱ组比较,Ⅲ组术后认知功能障碍发生率降低,T～T4时单核细胞TLR2和TLR4表达下调(P＜0.05).结论 右美托咪啶可预防老年患者POCD的发生,其机制与抑制单核细胞TLR2和TLR4的表达有关.     

山莨菪碱对过度训练大鼠肾小管上皮细胞Toll样受体4表达的影响

目的 评价山莨菪碱对过度训练大鼠肾小管上皮细胞Toll样受体4(TLR4)表达的影响.方法 雄性SD大鼠48只,体重200～220 g,采用随机数字表法,将其随机分为3组:正常对照组(C组,n=8)、力竭运动组(E组,n=24)和山莨菪碱组(A组,n=16).采用大鼠游泳至力竭建立过度训练模型,A组于力竭运动前20 min腹腔注射山莨菪碱10 mg/kg后进行力竭运动.检测肾组织细胞凋亡和肾小管上皮细胞TLR4蛋白、TLR4 mRNA的表达水平.结果 与C组比较,E组和A组细胞凋亡率升高,肾小管上皮细胞TLR4蛋白和TLR4 mRNA表达上调(P＜0.05);与E组比较,A组细胞凋亡率降低,肾小管上皮细胞TLR4蛋白和TLR4 mRNA表达下调(P＜0.05).结论 山莨菪碱可通过下调过度训练大鼠肾小管上皮细胞TLR4表达,抑制肾脏细胞凋亡.