A Review The diseases caused by endotoxin have seriously affected human health. Previous studies have shown that p38 MAPK pathway is involved in the intracellular signal transduction induced by lipopolysaccharide (LPS...A Review The diseases caused by endotoxin have seriously affected human health. Previous studies have shown that p38 MAPK pathway is involved in the intracellular signal transduction induced by lipopolysaccharide (LPS), which plays an important role in the activation of inflammation-related cells to release inflammation mediator. Recently there have been some progresses in the isoforms distribution, substrate, molecular mechanism of regulating the release of inflammatory mediators, cellular specific activation and levels of p38 MAPK. [展开更多
目的探讨背根神经节(DRG)神经元P2X3受体在神经病理痛(NP)大鼠疾病发生和进展中的作用,并分析其与磷酸化丝裂原活化蛋白激酶p38(p38 MAPK)的相关性。方法60只大鼠采用体质量排序法随机分为假手术组、模型组、P2X3受体拮抗剂组、P2X3受...目的探讨背根神经节(DRG)神经元P2X3受体在神经病理痛(NP)大鼠疾病发生和进展中的作用,并分析其与磷酸化丝裂原活化蛋白激酶p38(p38 MAPK)的相关性。方法60只大鼠采用体质量排序法随机分为假手术组、模型组、P2X3受体拮抗剂组、P2X3受体激动剂组4组,每组各15只。采用坐骨神经缩窄性损伤法建立NP大鼠模型,假手术组仅分离坐骨神经不结扎。建模成功大鼠假手术组14只、模型组12只,分别鞘内注射20μL无菌生理盐水;P2X3受体拮抗剂组12只,鞘内注射10μL无菌生理盐水+10μL A-317491;P2X3受体激动剂组13只,鞘内注射10μL无菌生理盐水+10μL ATP。评估各组大鼠手术前后各时间点热刺激缩足反射潜伏期(PWTL)、机械缩足反射阈值(MWT);检测各组术后7、14 d DRG中P2X3受体、p-p38MAPK蛋白表达情况,并采用Pearson相关性系数法分析P2X3受体与p-p38MAPK的相关性。结果模型组术后患肢出现明显痛觉过敏体征,P2X3受体激动剂组更为严重,P2X3受体拮抗剂组有所改善。与假手术组比较,模型组、P2X3受体拮抗剂组、P2X3受体激动剂组术后1 d PWTL较术前缩短,且术后1~14 d保持平稳(P<0.05);与模型组比较,术后1~14 d P2X3受体拮抗剂组PWTL均延长,P2X3受体激动剂组均缩短,但模型组、P2X3受体拮抗剂组、P2X3受体激动组仍短于假手术组(P<0.05)。模型组、P2X3受体拮抗剂组、P2X3受体激动剂组术后1 d开始MWT降低,且分别于术后14、7 d降至最低(P<0.05);与模型组比较,术后1~14 d P2X3受体拮抗剂组MWT均升高,P2X3受体激动剂MWT均降低,但模型组、P2X3受体拮抗剂组、P2X3受体激动组仍低于假手术组(P<0.05)。与模型组比较,P2X3受体拮抗剂组术后7、14 d DRG中P2X3受体、p-p38MAPK蛋白相对表达量均降低,P2X3受体激动剂组均升高,但模型组、P2X3受体拮抗剂组、P2X3受体激动组均高于假手术组(P<0.05)。经Pearson相关性分析,术后7、14 d DRG中P2X3受体相对表展开更多
Background Mucus hypersecretion in the respiratory tract and goblet cell metaplasia in the airway epithelium contribute to the morbidity and mortality associated with airway inflammatory diseases. This study aimed to ...Background Mucus hypersecretion in the respiratory tract and goblet cell metaplasia in the airway epithelium contribute to the morbidity and mortality associated with airway inflammatory diseases. This study aimed to examine the effect and mechanisms of simvastatin on airway mucus hypersecretion in rats treated with lipopolysaccharide （LPS）. Methods Mucus hypersecretion in rat airways was induced by intra-tracheal instillation of LPS. Rats treated with or without LPS were administered intra-peritoneally simvastatin （5 and 20 mg/kg） for 4 days. Expression of Muc5ac, RhoA and mitogen-activated protein kinases （MAPK） p38 in lung were detected by real-time polymerase chain reaction （PCR）, immunohistochemistry or Western blotting. Tumor necrosis factor （TNF）-α and IL-8 in bronchoalveolar lavage fluid （BALF） were assayed by an enzyme-linked lectin assay and enzyme linked immunosorbent assay （ELISA）. Results Simvastatin attenuated LPS-induced goblet cell hyperplasia in bronchial epithelium and Muc5ac hypersecretion at both the gene and protein levels in lung （P 〈0.05）. Moreover, simvastatin inhibited neutrophil accumulation and the increased concentration of TNF-α and IL-8 in BALF follows LPS stimulation （P 〈0.05）. The higher dose of simvastatin was associated with a more significant reduction in Muc5ac mRNA expression, neutrophil accumulation and inflammatory cytokine release. Simultaneously, the increased expression of RhoA and p38 MAPK were observed in LPS-treated lung （P 〈0.05）. Simvastatin inhibited the expression of RhoA and p38 phosphorylation in lung following LPS stimulation （P 〈0.05）. However, the increased expression of p38 protein in LPS-treated lung was not affected by simvastatin administration. Conclusions Simvastatin attenuates airway mucus hypersecretion and pulmonary inflammatory damage induced by LPS. The inhibitory effect of simvastatin on airway mucus hypersecretion may be through, at least in part, the suppression of neutrophil accumulation and 展开更多
文摘A Review The diseases caused by endotoxin have seriously affected human health. Previous studies have shown that p38 MAPK pathway is involved in the intracellular signal transduction induced by lipopolysaccharide (LPS), which plays an important role in the activation of inflammation-related cells to release inflammation mediator. Recently there have been some progresses in the isoforms distribution, substrate, molecular mechanism of regulating the release of inflammatory mediators, cellular specific activation and levels of p38 MAPK. [
文摘目的探讨背根神经节(DRG)神经元P2X3受体在神经病理痛(NP)大鼠疾病发生和进展中的作用,并分析其与磷酸化丝裂原活化蛋白激酶p38(p38 MAPK)的相关性。方法60只大鼠采用体质量排序法随机分为假手术组、模型组、P2X3受体拮抗剂组、P2X3受体激动剂组4组,每组各15只。采用坐骨神经缩窄性损伤法建立NP大鼠模型,假手术组仅分离坐骨神经不结扎。建模成功大鼠假手术组14只、模型组12只,分别鞘内注射20μL无菌生理盐水;P2X3受体拮抗剂组12只,鞘内注射10μL无菌生理盐水+10μL A-317491;P2X3受体激动剂组13只,鞘内注射10μL无菌生理盐水+10μL ATP。评估各组大鼠手术前后各时间点热刺激缩足反射潜伏期(PWTL)、机械缩足反射阈值(MWT);检测各组术后7、14 d DRG中P2X3受体、p-p38MAPK蛋白表达情况,并采用Pearson相关性系数法分析P2X3受体与p-p38MAPK的相关性。结果模型组术后患肢出现明显痛觉过敏体征,P2X3受体激动剂组更为严重,P2X3受体拮抗剂组有所改善。与假手术组比较,模型组、P2X3受体拮抗剂组、P2X3受体激动剂组术后1 d PWTL较术前缩短,且术后1~14 d保持平稳(P<0.05);与模型组比较,术后1~14 d P2X3受体拮抗剂组PWTL均延长,P2X3受体激动剂组均缩短,但模型组、P2X3受体拮抗剂组、P2X3受体激动组仍短于假手术组(P<0.05)。模型组、P2X3受体拮抗剂组、P2X3受体激动剂组术后1 d开始MWT降低,且分别于术后14、7 d降至最低(P<0.05);与模型组比较,术后1~14 d P2X3受体拮抗剂组MWT均升高,P2X3受体激动剂MWT均降低,但模型组、P2X3受体拮抗剂组、P2X3受体激动组仍低于假手术组(P<0.05)。与模型组比较,P2X3受体拮抗剂组术后7、14 d DRG中P2X3受体、p-p38MAPK蛋白相对表达量均降低,P2X3受体激动剂组均升高,但模型组、P2X3受体拮抗剂组、P2X3受体激动组均高于假手术组(P<0.05)。经Pearson相关性分析,术后7、14 d DRG中P2X3受体相对表
基金This study was supported by grants from National Natural Science Foundation of China to Dr. WEN Fu-qing （No. 30425007, 30370627, 30670921） and from China Medical Board of New York to Dr. WEN Fu-qiang （No. 0-722）.
文摘Background Mucus hypersecretion in the respiratory tract and goblet cell metaplasia in the airway epithelium contribute to the morbidity and mortality associated with airway inflammatory diseases. This study aimed to examine the effect and mechanisms of simvastatin on airway mucus hypersecretion in rats treated with lipopolysaccharide （LPS）. Methods Mucus hypersecretion in rat airways was induced by intra-tracheal instillation of LPS. Rats treated with or without LPS were administered intra-peritoneally simvastatin （5 and 20 mg/kg） for 4 days. Expression of Muc5ac, RhoA and mitogen-activated protein kinases （MAPK） p38 in lung were detected by real-time polymerase chain reaction （PCR）, immunohistochemistry or Western blotting. Tumor necrosis factor （TNF）-α and IL-8 in bronchoalveolar lavage fluid （BALF） were assayed by an enzyme-linked lectin assay and enzyme linked immunosorbent assay （ELISA）. Results Simvastatin attenuated LPS-induced goblet cell hyperplasia in bronchial epithelium and Muc5ac hypersecretion at both the gene and protein levels in lung （P 〈0.05）. Moreover, simvastatin inhibited neutrophil accumulation and the increased concentration of TNF-α and IL-8 in BALF follows LPS stimulation （P 〈0.05）. The higher dose of simvastatin was associated with a more significant reduction in Muc5ac mRNA expression, neutrophil accumulation and inflammatory cytokine release. Simultaneously, the increased expression of RhoA and p38 MAPK were observed in LPS-treated lung （P 〈0.05）. Simvastatin inhibited the expression of RhoA and p38 phosphorylation in lung following LPS stimulation （P 〈0.05）. However, the increased expression of p38 protein in LPS-treated lung was not affected by simvastatin administration. Conclusions Simvastatin attenuates airway mucus hypersecretion and pulmonary inflammatory damage induced by LPS. The inhibitory effect of simvastatin on airway mucus hypersecretion may be through, at least in part, the suppression of neutrophil accumulation and
