罗格列酮对人多囊肾囊肿衬里上皮细胞增殖的抑制作用

Objective To investigate the antiproliferative effect of rosiglitazone, a thiazolidinedione (TZD) on autosomal dominant polycystic kidney disease (ADPKD) cystic lining epithelial cells and to explore the underlying molecular mechanism. Methods ADPKD cysticlining immortalized epithelial (WT9-12) cells were stimulated by rosiglitazone with different concentrations. After treatment, MTT method was performed to detect the level of proliferation; flow cytometry was used to determine the cell cycle distribution and the apoptosis rate. Western blotting was used to detect the protein expressions of mTOR, p70S6K, 4E-Bp1, PPARγ PPARγ siRNA was transfected into WT9-12 cells to knock down the expression of PPARγ Results Treatment of WT9-12 cells with rosiglitazone resulted in a dose-dependent and time-dependent strong inhibition of cell proliferation, an accumulation of cells in the G0/G1 phase (rosiglitazone 50 μmol/L 65.43%,rosiglitazone 100 μmol/L 64.02%, control 49.65% ) and 6% apoptosis at high concentration (rosiglitazone 200 μmol/L). Rosiglitazone reduced the phosphorylation of p70S6K in a dosedependent and time-dependent manner. The levels of phosphorylated mTOR and 4E-Bp1, the latter being a downstream substrate of mTOR related mRNA translation initiation, were not changed by rosiglitazone. Cells were pre-incubated with GW9662, a PPARγ antagonist, before the treatment with rosiglitazone, the inhibition of p70S6 kinase phosphorylation by rosiglitazone was partially prevented by GW9662 (P＜0.01). Then PPARγ siRNA was transfected into WT9-12 cells, in contrast to untransfected control or cells transfected with an irrelevant siRNA, rosiglitazone did not cause an obvious inhibition of p70S6 kinase phosphorylation in PPARγ knock-down.Conclusion Rosiglitazone inhibits the proliferation of ADPKD cystic lining epithelial cells, and down-regulates p70S6 kinase phosphorylation through mTOR-independent and PPARγ-dependent signal pathway.     

罗格列酮对多囊肾囊肿衬里上皮细胞p38促分裂原活化蛋白激酶信号通路的影响

Objective To investigate the effect of rosiglitazone on p38 mitogen-activated protein kinase (p38MAPK) pathway in polycystic kidney cyst-lining epithelial cells. Methods The cyst-lining epithelial cells (PKD cells) from human polycystic kidney were treated with rosiglitazone (10 μmol/L), peroxisome proliferator-activated receptor-γ (PPARγ) inhibitor GW9662 (10 μmol/L), rosiglitazone (10 μmol/L) +GW9662 (10 μmol/L), p38MAPK specific inhibitor SB203580 (10 μmol/L), SB203580 (10 μmol/L)+ rosiglitazone(10 μmol/L) for 2 hours followed by epidermal growth factor (EGF) stimulation. Protein expressions of p38, phuspho-p38 (p-p38) and proliferating cell nuclear antigen (PCNA) were detected by Western blot. p38 mRNA was examined by RT-PCR. Expression of c-fos and c-jun was observed by immunocytochemistry. Results (1) EGF markedly up-regulated the expressions of p38, p-p38, PCNA, c-fos anti c-jun compared with control group (P<0.01). (2) Compared with EGF treated group, rosiglitazone significantly reduced p38 activation and mRNA expression (P<0.01, respectively). Rosiglitazone, rosiglitazone+SB203580 could significantly down-regulated p-p38, PCNA, c-fos and c-jun expression (P<0.01, respectively) with no significant difference between these two groups. (3) GW9662 partially reversed the reduction effect of rosiglitazone. Conclusions Rosiglitazone can inhibit proliferation of autosomal dominant polycystic kidney disease cyst-lining epithelial cells partially through down-regulating p38 activation and reducing c-fos, c-jun and PCNA expression. The above effect of rosiglitazone is in part PPARγ-independcnt.     

罗格列酮对多囊肾囊肿衬里上皮细胞p38促分裂原活化蛋白激酶信号通路的影响

Objective To investigate the effect of rosiglitazone on p38 mitogen-activated protein kinase (p38MAPK) pathway in polycystic kidney cyst-lining epithelial cells. Methods The cyst-lining epithelial cells (PKD cells) from human polycystic kidney were treated with rosiglitazone (10 μmol/L), peroxisome proliferator-activated receptor-γ (PPARγ) inhibitor GW9662 (10 μmol/L), rosiglitazone (10 μmol/L) +GW9662 (10 μmol/L), p38MAPK specific inhibitor SB203580 (10 μmol/L), SB203580 (10 μmol/L)+ rosiglitazone(10 μmol/L) for 2 hours followed by epidermal growth factor (EGF) stimulation. Protein expressions of p38, phuspho-p38 (p-p38) and proliferating cell nuclear antigen (PCNA) were detected by Western blot. p38 mRNA was examined by RT-PCR. Expression of c-fos and c-jun was observed by immunocytochemistry. Results (1) EGF markedly up-regulated the expressions of p38, p-p38, PCNA, c-fos anti c-jun compared with control group (P<0.01). (2) Compared with EGF treated group, rosiglitazone significantly reduced p38 activation and mRNA expression (P<0.01, respectively). Rosiglitazone, rosiglitazone+SB203580 could significantly down-regulated p-p38, PCNA, c-fos and c-jun expression (P<0.01, respectively) with no significant difference between these two groups. (3) GW9662 partially reversed the reduction effect of rosiglitazone. Conclusions Rosiglitazone can inhibit proliferation of autosomal dominant polycystic kidney disease cyst-lining epithelial cells partially through down-regulating p38 activation and reducing c-fos, c-jun and PCNA expression. The above effect of rosiglitazone is in part PPARγ-independcnt.     

罗格列酮对多囊肾囊肿衬里上皮细胞p38促分裂原活化蛋白激酶信号通路的影响

Objective To investigate the effect of rosiglitazone on p38 mitogen-activated protein kinase (p38MAPK) pathway in polycystic kidney cyst-lining epithelial cells. Methods The cyst-lining epithelial cells (PKD cells) from human polycystic kidney were treated with rosiglitazone (10 μmol/L), peroxisome proliferator-activated receptor-γ (PPARγ) inhibitor GW9662 (10 μmol/L), rosiglitazone (10 μmol/L) +GW9662 (10 μmol/L), p38MAPK specific inhibitor SB203580 (10 μmol/L), SB203580 (10 μmol/L)+ rosiglitazone(10 μmol/L) for 2 hours followed by epidermal growth factor (EGF) stimulation. Protein expressions of p38, phuspho-p38 (p-p38) and proliferating cell nuclear antigen (PCNA) were detected by Western blot. p38 mRNA was examined by RT-PCR. Expression of c-fos and c-jun was observed by immunocytochemistry. Results (1) EGF markedly up-regulated the expressions of p38, p-p38, PCNA, c-fos anti c-jun compared with control group (P<0.01). (2) Compared with EGF treated group, rosiglitazone significantly reduced p38 activation and mRNA expression (P<0.01, respectively). Rosiglitazone, rosiglitazone+SB203580 could significantly down-regulated p-p38, PCNA, c-fos and c-jun expression (P<0.01, respectively) with no significant difference between these two groups. (3) GW9662 partially reversed the reduction effect of rosiglitazone. Conclusions Rosiglitazone can inhibit proliferation of autosomal dominant polycystic kidney disease cyst-lining epithelial cells partially through down-regulating p38 activation and reducing c-fos, c-jun and PCNA expression. The above effect of rosiglitazone is in part PPARγ-independcnt.     

罗格列酮对多囊肾囊肿衬里上皮细胞p38促分裂原活化蛋白激酶信号通路的影响

Objective To investigate the effect of rosiglitazone on p38 mitogen-activated protein kinase (p38MAPK) pathway in polycystic kidney cyst-lining epithelial cells. Methods The cyst-lining epithelial cells (PKD cells) from human polycystic kidney were treated with rosiglitazone (10 μmol/L), peroxisome proliferator-activated receptor-γ (PPARγ) inhibitor GW9662 (10 μmol/L), rosiglitazone (10 μmol/L) +GW9662 (10 μmol/L), p38MAPK specific inhibitor SB203580 (10 μmol/L), SB203580 (10 μmol/L)+ rosiglitazone(10 μmol/L) for 2 hours followed by epidermal growth factor (EGF) stimulation. Protein expressions of p38, phuspho-p38 (p-p38) and proliferating cell nuclear antigen (PCNA) were detected by Western blot. p38 mRNA was examined by RT-PCR. Expression of c-fos and c-jun was observed by immunocytochemistry. Results (1) EGF markedly up-regulated the expressions of p38, p-p38, PCNA, c-fos anti c-jun compared with control group (P<0.01). (2) Compared with EGF treated group, rosiglitazone significantly reduced p38 activation and mRNA expression (P<0.01, respectively). Rosiglitazone, rosiglitazone+SB203580 could significantly down-regulated p-p38, PCNA, c-fos and c-jun expression (P<0.01, respectively) with no significant difference between these two groups. (3) GW9662 partially reversed the reduction effect of rosiglitazone. Conclusions Rosiglitazone can inhibit proliferation of autosomal dominant polycystic kidney disease cyst-lining epithelial cells partially through down-regulating p38 activation and reducing c-fos, c-jun and PCNA expression. The above effect of rosiglitazone is in part PPARγ-independcnt.     

罗格列酮对多囊肾囊肿衬里上皮细胞p38促分裂原活化蛋白激酶信号通路的影响

Objective To investigate the effect of rosiglitazone on p38 mitogen-activated protein kinase (p38MAPK) pathway in polycystic kidney cyst-lining epithelial cells. Methods The cyst-lining epithelial cells (PKD cells) from human polycystic kidney were treated with rosiglitazone (10 μmol/L), peroxisome proliferator-activated receptor-γ (PPARγ) inhibitor GW9662 (10 μmol/L), rosiglitazone (10 μmol/L) +GW9662 (10 μmol/L), p38MAPK specific inhibitor SB203580 (10 μmol/L), SB203580 (10 μmol/L)+ rosiglitazone(10 μmol/L) for 2 hours followed by epidermal growth factor (EGF) stimulation. Protein expressions of p38, phuspho-p38 (p-p38) and proliferating cell nuclear antigen (PCNA) were detected by Western blot. p38 mRNA was examined by RT-PCR. Expression of c-fos and c-jun was observed by immunocytochemistry. Results (1) EGF markedly up-regulated the expressions of p38, p-p38, PCNA, c-fos anti c-jun compared with control group (P<0.01). (2) Compared with EGF treated group, rosiglitazone significantly reduced p38 activation and mRNA expression (P<0.01, respectively). Rosiglitazone, rosiglitazone+SB203580 could significantly down-regulated p-p38, PCNA, c-fos and c-jun expression (P<0.01, respectively) with no significant difference between these two groups. (3) GW9662 partially reversed the reduction effect of rosiglitazone. Conclusions Rosiglitazone can inhibit proliferation of autosomal dominant polycystic kidney disease cyst-lining epithelial cells partially through down-regulating p38 activation and reducing c-fos, c-jun and PCNA expression. The above effect of rosiglitazone is in part PPARγ-independcnt.     

罗格列酮对多囊肾囊肿衬里上皮细胞p38促分裂原活化蛋白激酶信号通路的影响

Objective To investigate the effect of rosiglitazone on p38 mitogen-activated protein kinase (p38MAPK) pathway in polycystic kidney cyst-lining epithelial cells. Methods The cyst-lining epithelial cells (PKD cells) from human polycystic kidney were treated with rosiglitazone (10 μmol/L), peroxisome proliferator-activated receptor-γ (PPARγ) inhibitor GW9662 (10 μmol/L), rosiglitazone (10 μmol/L) +GW9662 (10 μmol/L), p38MAPK specific inhibitor SB203580 (10 μmol/L), SB203580 (10 μmol/L)+ rosiglitazone(10 μmol/L) for 2 hours followed by epidermal growth factor (EGF) stimulation. Protein expressions of p38, phuspho-p38 (p-p38) and proliferating cell nuclear antigen (PCNA) were detected by Western blot. p38 mRNA was examined by RT-PCR. Expression of c-fos and c-jun was observed by immunocytochemistry. Results (1) EGF markedly up-regulated the expressions of p38, p-p38, PCNA, c-fos anti c-jun compared with control group (P<0.01). (2) Compared with EGF treated group, rosiglitazone significantly reduced p38 activation and mRNA expression (P<0.01, respectively). Rosiglitazone, rosiglitazone+SB203580 could significantly down-regulated p-p38, PCNA, c-fos and c-jun expression (P<0.01, respectively) with no significant difference between these two groups. (3) GW9662 partially reversed the reduction effect of rosiglitazone. Conclusions Rosiglitazone can inhibit proliferation of autosomal dominant polycystic kidney disease cyst-lining epithelial cells partially through down-regulating p38 activation and reducing c-fos, c-jun and PCNA expression. The above effect of rosiglitazone is in part PPARγ-independcnt.     

罗格列酮对多囊肾囊肿衬里上皮细胞p38促分裂原活化蛋白激酶信号通路的影响

Objective To investigate the effect of rosiglitazone on p38 mitogen-activated protein kinase (p38MAPK) pathway in polycystic kidney cyst-lining epithelial cells. Methods The cyst-lining epithelial cells (PKD cells) from human polycystic kidney were treated with rosiglitazone (10 μmol/L), peroxisome proliferator-activated receptor-γ (PPARγ) inhibitor GW9662 (10 μmol/L), rosiglitazone (10 μmol/L) +GW9662 (10 μmol/L), p38MAPK specific inhibitor SB203580 (10 μmol/L), SB203580 (10 μmol/L)+ rosiglitazone(10 μmol/L) for 2 hours followed by epidermal growth factor (EGF) stimulation. Protein expressions of p38, phuspho-p38 (p-p38) and proliferating cell nuclear antigen (PCNA) were detected by Western blot. p38 mRNA was examined by RT-PCR. Expression of c-fos and c-jun was observed by immunocytochemistry. Results (1) EGF markedly up-regulated the expressions of p38, p-p38, PCNA, c-fos anti c-jun compared with control group (P<0.01). (2) Compared with EGF treated group, rosiglitazone significantly reduced p38 activation and mRNA expression (P<0.01, respectively). Rosiglitazone, rosiglitazone+SB203580 could significantly down-regulated p-p38, PCNA, c-fos and c-jun expression (P<0.01, respectively) with no significant difference between these two groups. (3) GW9662 partially reversed the reduction effect of rosiglitazone. Conclusions Rosiglitazone can inhibit proliferation of autosomal dominant polycystic kidney disease cyst-lining epithelial cells partially through down-regulating p38 activation and reducing c-fos, c-jun and PCNA expression. The above effect of rosiglitazone is in part PPARγ-independcnt.     

罗格列酮对多囊肾囊肿衬里上皮细胞p38促分裂原活化蛋白激酶信号通路的影响

Objective To investigate the effect of rosiglitazone on p38 mitogen-activated protein kinase (p38MAPK) pathway in polycystic kidney cyst-lining epithelial cells. Methods The cyst-lining epithelial cells (PKD cells) from human polycystic kidney were treated with rosiglitazone (10 μmol/L), peroxisome proliferator-activated receptor-γ (PPARγ) inhibitor GW9662 (10 μmol/L), rosiglitazone (10 μmol/L) +GW9662 (10 μmol/L), p38MAPK specific inhibitor SB203580 (10 μmol/L), SB203580 (10 μmol/L)+ rosiglitazone(10 μmol/L) for 2 hours followed by epidermal growth factor (EGF) stimulation. Protein expressions of p38, phuspho-p38 (p-p38) and proliferating cell nuclear antigen (PCNA) were detected by Western blot. p38 mRNA was examined by RT-PCR. Expression of c-fos and c-jun was observed by immunocytochemistry. Results (1) EGF markedly up-regulated the expressions of p38, p-p38, PCNA, c-fos anti c-jun compared with control group (P<0.01). (2) Compared with EGF treated group, rosiglitazone significantly reduced p38 activation and mRNA expression (P<0.01, respectively). Rosiglitazone, rosiglitazone+SB203580 could significantly down-regulated p-p38, PCNA, c-fos and c-jun expression (P<0.01, respectively) with no significant difference between these two groups. (3) GW9662 partially reversed the reduction effect of rosiglitazone. Conclusions Rosiglitazone can inhibit proliferation of autosomal dominant polycystic kidney disease cyst-lining epithelial cells partially through down-regulating p38 activation and reducing c-fos, c-jun and PCNA expression. The above effect of rosiglitazone is in part PPARγ-independcnt.     

罗格列酮对多囊肾囊肿衬里上皮细胞p38促分裂原活化蛋白激酶信号通路的影响

Objective To investigate the effect of rosiglitazone on p38 mitogen-activated protein kinase (p38MAPK) pathway in polycystic kidney cyst-lining epithelial cells. Methods The cyst-lining epithelial cells (PKD cells) from human polycystic kidney were treated with rosiglitazone (10 μmol/L), peroxisome proliferator-activated receptor-γ (PPARγ) inhibitor GW9662 (10 μmol/L), rosiglitazone (10 μmol/L) +GW9662 (10 μmol/L), p38MAPK specific inhibitor SB203580 (10 μmol/L), SB203580 (10 μmol/L)+ rosiglitazone(10 μmol/L) for 2 hours followed by epidermal growth factor (EGF) stimulation. Protein expressions of p38, phuspho-p38 (p-p38) and proliferating cell nuclear antigen (PCNA) were detected by Western blot. p38 mRNA was examined by RT-PCR. Expression of c-fos and c-jun was observed by immunocytochemistry. Results (1) EGF markedly up-regulated the expressions of p38, p-p38, PCNA, c-fos anti c-jun compared with control group (P<0.01). (2) Compared with EGF treated group, rosiglitazone significantly reduced p38 activation and mRNA expression (P<0.01, respectively). Rosiglitazone, rosiglitazone+SB203580 could significantly down-regulated p-p38, PCNA, c-fos and c-jun expression (P<0.01, respectively) with no significant difference between these two groups. (3) GW9662 partially reversed the reduction effect of rosiglitazone. Conclusions Rosiglitazone can inhibit proliferation of autosomal dominant polycystic kidney disease cyst-lining epithelial cells partially through down-regulating p38 activation and reducing c-fos, c-jun and PCNA expression. The above effect of rosiglitazone is in part PPARγ-independcnt.     

自噬信号因子P70S6K参与Cox7a2调控睾酮生成机制研究

目的:研究Cox7a2对TM3 Leydig细胞睾酮生成的影响以及涉及其中的自噬调控信号的作用。方法:构建Cox7a2荧光表达载体,转染TM3 Leydig细胞。ELISA测定睾酮水平,Western印迹检测Cox7a2对睾酮合成快速调节蛋白StAR表达和自噬调控因子P70S6K磷酸化水平的影响。结果:在TM3 Leydig细胞中,LH刺激能增加促进StAR蛋白表达,增加睾酮合成水平。Cox7a2在TM3小鼠睾丸Leydig细胞中抑制P70S6K磷酸化水平,降低StAR蛋白的表达,进而抑制LH诱导的睾酮合成。结论:Cox7a2通过抑制快速调节蛋白StAR的表达减少LH诱导的睾酮分泌,这至少和Cox7a2抑制自噬调控因子P70S6K有关。     

mTOR信号通路在Xp11.2易位/TFE3基因融合相关性肾癌中的表达及其意义

目的:探讨mTOR信号通路在Xp11.2易位/TFE3基因融合相关性肾癌(简称TFE3肾细胞癌)中的表达及其意义。方法:选取TFE3肾细胞癌23例、肾透明细胞癌组织60例和乳头状肾细胞癌20例。采用免疫组化方法检测3种肾细胞癌组织中p-mTOR与P70S6K的表达情况,观察二者表达与3种肾细胞癌的关系,进而研究mTOR信号通路与TFE3肾细胞癌发生发展的关系。结果:p-mTOR在TFE3肾细胞癌、肾透明细胞癌和乳头状肾细胞癌中的表达分别为(83.7±3.2)、(49.5±6.7)和(46.8±5.3)(P<0.05)。P70S6K在TFE3肾细胞癌、乳头状肾细胞癌组和肾透明细胞癌中的表达分别为(88.2±9.8)、(42.7±6.7)和(52.4±7.1)(P<0.05)。p-mTOR在年龄<35岁组和年龄≥35岁组的TFE3肾细胞癌表达为(212.0±75.9)和(27.3±47.5),在有淋巴结转移组和无淋巴结转移组表达为(255.0±21.2)和(72.1±93.4),在有脉管瘤栓组和无脉管瘤栓组表达为(225.0±35.5)和(81.6±89.4),两组比较差异均有统计学意义(P<0.05)。P70S6K在年龄<35岁组和年龄≥35岁组的TFE3肾细胞癌组织中的表达为(220.0±63.2)和(30.3±49.7),在有淋巴结转移组和无淋巴结转移组表达为(187.0±47.5)和(45.1±73.6),在有脉管瘤栓组和无脉管瘤栓组表达为(240.0±42.4)和(73.5±95.9),两组比较差异均有统计学意义(P<0.05)。TFE3肾细胞癌组织中p-mTOR和P70S6K表达的H-score评分呈正相关(r=0.987,P<0.05)。结论:与肾透明细胞癌和乳头状肾细胞癌组织相比,TFE3肾细胞癌组织中pmTOR与P70S6K表达显著增高,有助于TFE3肾细胞癌的鉴别诊断。TFE3肾细胞癌中P70S6K和p-mTOR表达与患者年龄、脉管瘤栓和淋巴结转移等因素相关,而与肿瘤直径大小和性别无关。TFE3肾细胞癌中mTOR信号通路处于激活状态,为TFE3肾细胞癌的分子治疗提示潜在作用靶点。     

mTOR/P70S6K信号通路活化在肝硬化门静脉高压症中意义的实验研究

目的 探讨mTOR/P70S6K信号通路在早期肝硬化门静脉高压症中的活化状态,证实mTOR信号通路的激活参与肝硬化门静脉高压症的发病,并探讨其可能机制.方法 本实验采用胆道结扎离断制备大鼠肝硬化门静脉高压症模型.雄性SD大鼠20只随机分为假手术组和模型组.通过组织病理学、形态学和血流动力学评估肝纤维化、炎症、和门静脉压力.采用RT-PCR和Western blot法分别测定肝纤维化标志物PC-αⅠ、α-SMA、TGFβ1及PDGF基因的转录和mTOR信号通路标志物P70S6K和磷酸化的P70S6K(P-P70S6K)的表达.结果 模型组大鼠胆道结扎离断3周后,P-P70S6K表达量明显增高而总蛋白P70S6K无显著差异,同时HSCs和胆管细胞活化增殖显著,肝脏促纤维化基因明显上调,间质胶原合成增加.结论 mTOR/P70S6K信号通路主要以磷酸化功能状态参与肝硬化门静脉高压症的形成,阻断该通路可能成为肝硬化门静脉高压症治疗的新靶向.     

罗格列酮对人多囊肾囊肿衬里上皮细胞增殖的抑制作用

目的 探讨过氧化物酶体增殖物激活受体γ（PPARγ）激动剂罗格列酮对常染色体显性遗传性多囊肾病（ADPKD）囊肿衬里上皮细胞增殖的抑制作用及其机制。 方法 MTT法检测罗格列酮对ADPKD囊肿衬里上皮细胞系（WT9-12）细胞增殖的作用;流式细胞术检测罗格列酮对WT9-12细胞周期及凋亡的影响;Western印迹法检测罗格列酮对哺乳类动物的雷帕霉素靶蛋白（mTOR）-p70核糖体S6激酶（p70S6K）信号通路的影响。给予PPARγ特异性抑制剂GW9662及PPARγ siRNA瞬时转染WT9-12细胞,检测罗格列酮对细胞增殖及对mTOR信号通路的作用是否为PPARγ依赖性的。 结果 罗格列酮抑制WT9-12细胞增殖,此作用在0~200 &#61549;mol/L范围内呈剂量依赖性及时间依赖性,作用72 h的50%抑制率浓度为100 &#61549;mol/L。细胞周期分析显示,罗格列酮（50、100 &#61549;mol/L）作用后,G0/G1期细胞较对照组显著增多（65.43%、64.02%比49.65%,P ＜ 0.05）。50、100 &#61549;mol/L罗格列酮对细胞凋亡影响不大,高浓度（200 &#61549;mol/L）罗格列酮可使凋亡细胞达6%（正常对照组为4%）。罗格列酮可呈时间及剂量依赖性下调WT9-12细胞p70S6K磷酸化表达,而对mTOR及其另一个下游4E结合蛋白1（4E-BP1）磷酸化水平无明显影响。加入GW9662及转染PPARγ siRNA阻断PPARγ表达后,可部分阻断罗格列酮对p70S6K磷酸化的影响（P ＜ 0.01）。 结论 罗格列酮可抑制ADPKD囊肿衬里上皮细胞增殖和阻滞细胞周期,可不依赖于mTOR途径直接下调p70S6K磷酸化表达。罗格列酮对ADPKD囊肿衬里上皮细胞p70S6K磷酸化的影响是PPARγ依赖性的。     

帕瑞昔布钠超前镇痛对烧伤患者热休克蛋白70和白细胞介素-6水平的影响

目的 研究帕瑞昔布钠超前镇痛对烧伤患者的镇痛作用以及对热休克蛋白70(HSP70)、白细胞介素-6(IL-6)水平的影响.方法 全身麻醉下行削痂植皮术患者60例,随机均分为三组:P组麻醉诱导前30 min静脉给予帕瑞昔布钠40 mg,PD组分别于麻醉诱导前30 min和手术结束前静脉给予帕瑞昔布钠40 mg,N组手术结束前30 min静脉给予生理盐水5 ml.检测患者麻醉前、术毕、术后6、12、24 h血浆HSP70和IL-6水平.观察患者术后2、4、8、12、24 h的VAS评分.结果 术后4、8、12、24hP组和PD组VAS评分均低于N组(P＜0.05).术后6、12h P组和PD组HSP70显著升高(P＜0.05),且明显高于N组(P＜0.05).术后6、12、24h P组和PD组IL-6明显降低(P＜0.05),N组明显升高(P＜0.05),且明显高于P组和PD组(P＜0.05).结论 帕瑞昔布钠超前镇痛能够增加烧伤患者HSP70的浓度,减少炎性因子IL-6的释放,并产生较好的镇痛效果.     

不同镇痛方法对子宫切除术后病人血清细胞因子和HSP70水平的影响

目的 评价不同镇痛方法对子宫切除术后患者血清细胞因子IL-6、IL-10和热休克蛋白70（HSP70）水平的影响。方法 择期行子宫切除术患者48例，随机分为4组（n=12）；术后分别采用罗哌卡因混合芬太尼硬膜外镇痛（Ⅰ组）；芬太尼静脉镇痛（Ⅱ组）；罗哌卡因混合曲马多硬膜外镇痛（Ⅲ组）；曲马多静脉镇痛（Ⅳ组）。所有患者均行硬膜外麻醉，手术关腹时开始病人自控镇痛（PCA），均以LCP模式给药：负荷剂量5ml＋背景剂量lml／h＋PCA剂量1ml，锁定时间10min。检测麻醉前、术后2、24、48和72h时患者血清IL-6、IL-10和HSP70水平。结果四组术后VAS评分均在4分以下，术后患者血清IL-6、IL-10和HSP70水平均升高。术后24h，Ⅰ、Ⅲ组血清IL-6和HSP70水平低于Ⅱ、Ⅳ组（P〈0，01）；术后2、24h，Ⅳ组血清IL-10水平高于其它各组，且Ⅳ组IL-6／IL-10小于Ⅱ组（P〈0．05）。结论 硬膜外镇痛较静脉镇痛更能有效地降低子宫切除术后患者血清IL-6和HSP70水平升高程度。硬膜外罗哌卡因复合曲马多更适合用于术后镇痛。     

热休克蛋白70家族的功能和在神经保护中的作用

脑缺血耐受的实验研究发现,诱导热休克蛋白70家族(HSP70)的表达增加可能是内源性脑保护机制之一。HSP70包括两种蛋白:Hsp70(诱导型)和Hsc70(结构型)。本文就这两种蛋白的功能、表达的调节及在不同应激反应中表达的相关性作一综述。