枸杞多糖对MIN6细胞增殖活性和凋亡的影响

目的 研究不同浓度枸杞多糖对小鼠胰岛β细胞系MIN6细胞增殖活性和凋亡的影响.方法 培养MIN6细胞,分为对照组、不同浓度枸杞多糖干预组,分别给予0,100,200,400 mg/L枸杞多糖干预24 h.噻唑蓝(MTT)法检测MIN6细胞增殖活性,流式细胞术检测MIN6细胞凋亡率,Western印迹分析磷酸化细胞外信号调节激酶(ERK)及B淋巴细胞瘤-2(Bcl-2)蛋白表达.结果 与对照组相比,100、200 mg/L枸杞多糖干预组MIN6细胞增殖显著增加(P均＜0.01),MIN6细胞凋亡显著受抑制(P均＜0.01),而400 mg/L枸杞多糖干预组细胞增殖活性降低(P＜0.05),MIN6细胞凋亡增加(P＜0.01).Western印迹显示,与对照组相比,100,200,400 mg/L枸杞多糖干预组Bcl-2表达(F=65.26,P＜0.01)及磷酸化ERK水平(F=14.85,P＜0.01)均增加,而400 mg/L枸杞多糖干预组Bcl-2与磷酸化ERK表达下降(P均＜0.05),200 mg/L枸杞多糖干预组与400 mg/L枸杞多糖干预组相比,Bcl-2与磷酸化ERK水平差异均有统计学意义(P均＜0.01).结论 低浓度枸杞多糖可促进MIN6细胞增殖,减少MIN6细胞凋亡,而高浓度枸杞多糖作用相反,其机制可能与ERK信号通路有关.     

吡格列酮预防非肥胖糖尿病鼠胰岛β细胞凋亡的机制研究

目的 探讨吡格列酮预防非肥胖糖尿病小鼠胰岛β细胞凋亡的机制.方法 (1)将4周龄NOD雌鼠分为吡格列酮(21只)及对照(21只)组,分别摄食含0.02％吡格列酮的混合饲料和普通营养饲料.观察52周龄的累积糖尿病发病率.(2)各组取12周龄未发病NOD鼠(n=15)胰腺,HE染色观察胰岛炎;TUNEL+SABC法检测胰岛β细胞凋亡.(3)ELISA法测定血清、脾细胞培养上清IFN-γ和IL-4水平及培养脾细胞核因子PPARγ、NF-κB活性.结果 (1)30、52周龄时,吡格列酮及对照组发病率分别为57.1％和76.2％ 、76.2％和90.5％(均P＞0.05);15周龄时,吡格列酮及对照组发病率分别为4.8％和33.3％(P=0.045).(2) 12周龄时,吡格列酮组正常胰岛和胰岛周围炎比例(14.73％,26.02％)高于对照组(5.69％,15.72％;均P＜0.01),胰岛内炎比例(59.25％)则低于对照组(78.59％,P＜0.01);吡格列酮组胰岛β细胞凋亡率(6.17％±3.62％)低于对照组( 10.62％±4.43％,P=0.008).(3)12周龄NOD鼠吡格列酮组血清IFN-γ水平[(561.05 ±78.61) pg/ml]显著低于对照组[(666.43±28.42) pg/ml,P=0.045];在培养的脾细胞上清中,吡格列酮组IFN-γ水平[(605.84±65.60) pg/ml]显著低于对照组[(692.20±44.98)pg/ml,P=0.041].(4)在培养的脾细胞中,吡格列酮组PPARγ活性(0.06±0.01)高于对照组(0.03±0.01,P=0.013),NF-κB活性(0.03±0.01)较对照显著降低(0.08±0.01,P=0.001).结论 吡格列酮活化PPARγ,抑制NF-κB活性,血清和脾细胞上清IFN-γ下降,Th细胞向Th1方向分化减少,NOD鼠胰岛炎减轻、胰岛β细胞凋亡减少.     

大剂量阿托伐他汀预防对比剂肾病

Objective To compare the efficacy of high and low dose atorvastatin on preventing contrast induced nephropathy (CIN) in patients underwent diagnostic and therapeutic coronary intervention. Methods All patients received atorvastatin 10 mg/d on the basis of hydrated therapy (n =100) and high dose group received additional atorvastatin 80 nag at 12 to 24 hours before procedure (n =50). Scr, Ccr, blood β2-M, urine NAG/Cr, and urine osmolality before and after the procedure were compared between the groups. Results Baseline demographic characteristics and nephropathy risk factors were similar between groups. Cer was significantly reduced while blood β2-M and uric NAG/Cr were significantly increased in low dose group (all P ＜ 0.05) . Blood β2-M in the high dose group was significantly lower than that in the low dose group at day 1 [(2.35±0.52) mg/L vs. (2.67±0.64) mg/L, P =0.008], day 3[(2.49±0.55)mg/L vs. (2.80±0.64) mg/L,P =0.011] and day 5[(2.29±0.53) mg/L vs. (2.56±0.66) nag/L, P = 0.026] post-procedure respectively; urine NAG/Cr in the high dose group was also significantly lower than that in the low dose group at day 1 [(1.19±0.30) U/mmol vs. (1.46±0.34) U/mmol, P ＜ 0.001], day 3 [(1.30±0.30) U/mmol vs. (1.59±0.33) U/mmol, P ＜ 0.001], and day 5 [(1.10±0.30) U/mmol vs. (1.34±0.35) U/mmol, P = 0.001] post-procedure respectively;Cer in the high dose group was significantly higher than that in the low dose group at day 1 [(73.69±20.99) mL/min vs. (65.19±18.72) mL/min,P =0.035], day 3[(64.04±15.82) ml/min vs. (56.79±14.50)ml/min,P =0.019] post-procedure respectively. Conclusion High dose atorvastatin use before angiography is superior than low dose atorvastatin on attenuating contrast induced renal dysfunction.     

大剂量阿托伐他汀预防对比剂肾病

Objective To compare the efficacy of high and low dose atorvastatin on preventing contrast induced nephropathy (CIN) in patients underwent diagnostic and therapeutic coronary intervention. Methods All patients received atorvastatin 10 mg/d on the basis of hydrated therapy (n =100) and high dose group received additional atorvastatin 80 nag at 12 to 24 hours before procedure (n =50). Scr, Ccr, blood β2-M, urine NAG/Cr, and urine osmolality before and after the procedure were compared between the groups. Results Baseline demographic characteristics and nephropathy risk factors were similar between groups. Cer was significantly reduced while blood β2-M and uric NAG/Cr were significantly increased in low dose group (all P ＜ 0.05) . Blood β2-M in the high dose group was significantly lower than that in the low dose group at day 1 [(2.35±0.52) mg/L vs. (2.67±0.64) mg/L, P =0.008], day 3[(2.49±0.55)mg/L vs. (2.80±0.64) mg/L,P =0.011] and day 5[(2.29±0.53) mg/L vs. (2.56±0.66) nag/L, P = 0.026] post-procedure respectively; urine NAG/Cr in the high dose group was also significantly lower than that in the low dose group at day 1 [(1.19±0.30) U/mmol vs. (1.46±0.34) U/mmol, P ＜ 0.001], day 3 [(1.30±0.30) U/mmol vs. (1.59±0.33) U/mmol, P ＜ 0.001], and day 5 [(1.10±0.30) U/mmol vs. (1.34±0.35) U/mmol, P = 0.001] post-procedure respectively;Cer in the high dose group was significantly higher than that in the low dose group at day 1 [(73.69±20.99) mL/min vs. (65.19±18.72) mL/min,P =0.035], day 3[(64.04±15.82) ml/min vs. (56.79±14.50)ml/min,P =0.019] post-procedure respectively. Conclusion High dose atorvastatin use before angiography is superior than low dose atorvastatin on attenuating contrast induced renal dysfunction.     

大剂量阿托伐他汀预防对比剂肾病

Objective To compare the efficacy of high and low dose atorvastatin on preventing contrast induced nephropathy (CIN) in patients underwent diagnostic and therapeutic coronary intervention. Methods All patients received atorvastatin 10 mg/d on the basis of hydrated therapy (n =100) and high dose group received additional atorvastatin 80 nag at 12 to 24 hours before procedure (n =50). Scr, Ccr, blood β2-M, urine NAG/Cr, and urine osmolality before and after the procedure were compared between the groups. Results Baseline demographic characteristics and nephropathy risk factors were similar between groups. Cer was significantly reduced while blood β2-M and uric NAG/Cr were significantly increased in low dose group (all P ＜ 0.05) . Blood β2-M in the high dose group was significantly lower than that in the low dose group at day 1 [(2.35±0.52) mg/L vs. (2.67±0.64) mg/L, P =0.008], day 3[(2.49±0.55)mg/L vs. (2.80±0.64) mg/L,P =0.011] and day 5[(2.29±0.53) mg/L vs. (2.56±0.66) nag/L, P = 0.026] post-procedure respectively; urine NAG/Cr in the high dose group was also significantly lower than that in the low dose group at day 1 [(1.19±0.30) U/mmol vs. (1.46±0.34) U/mmol, P ＜ 0.001], day 3 [(1.30±0.30) U/mmol vs. (1.59±0.33) U/mmol, P ＜ 0.001], and day 5 [(1.10±0.30) U/mmol vs. (1.34±0.35) U/mmol, P = 0.001] post-procedure respectively;Cer in the high dose group was significantly higher than that in the low dose group at day 1 [(73.69±20.99) mL/min vs. (65.19±18.72) mL/min,P =0.035], day 3[(64.04±15.82) ml/min vs. (56.79±14.50)ml/min,P =0.019] post-procedure respectively. Conclusion High dose atorvastatin use before angiography is superior than low dose atorvastatin on attenuating contrast induced renal dysfunction.     

大剂量阿托伐他汀预防对比剂肾病

Objective To compare the efficacy of high and low dose atorvastatin on preventing contrast induced nephropathy (CIN) in patients underwent diagnostic and therapeutic coronary intervention. Methods All patients received atorvastatin 10 mg/d on the basis of hydrated therapy (n =100) and high dose group received additional atorvastatin 80 nag at 12 to 24 hours before procedure (n =50). Scr, Ccr, blood β2-M, urine NAG/Cr, and urine osmolality before and after the procedure were compared between the groups. Results Baseline demographic characteristics and nephropathy risk factors were similar between groups. Cer was significantly reduced while blood β2-M and uric NAG/Cr were significantly increased in low dose group (all P ＜ 0.05) . Blood β2-M in the high dose group was significantly lower than that in the low dose group at day 1 [(2.35±0.52) mg/L vs. (2.67±0.64) mg/L, P =0.008], day 3[(2.49±0.55)mg/L vs. (2.80±0.64) mg/L,P =0.011] and day 5[(2.29±0.53) mg/L vs. (2.56±0.66) nag/L, P = 0.026] post-procedure respectively; urine NAG/Cr in the high dose group was also significantly lower than that in the low dose group at day 1 [(1.19±0.30) U/mmol vs. (1.46±0.34) U/mmol, P ＜ 0.001], day 3 [(1.30±0.30) U/mmol vs. (1.59±0.33) U/mmol, P ＜ 0.001], and day 5 [(1.10±0.30) U/mmol vs. (1.34±0.35) U/mmol, P = 0.001] post-procedure respectively;Cer in the high dose group was significantly higher than that in the low dose group at day 1 [(73.69±20.99) mL/min vs. (65.19±18.72) mL/min,P =0.035], day 3[(64.04±15.82) ml/min vs. (56.79±14.50)ml/min,P =0.019] post-procedure respectively. Conclusion High dose atorvastatin use before angiography is superior than low dose atorvastatin on attenuating contrast induced renal dysfunction.     

大剂量阿托伐他汀预防对比剂肾病

Objective To compare the efficacy of high and low dose atorvastatin on preventing contrast induced nephropathy (CIN) in patients underwent diagnostic and therapeutic coronary intervention. Methods All patients received atorvastatin 10 mg/d on the basis of hydrated therapy (n =100) and high dose group received additional atorvastatin 80 nag at 12 to 24 hours before procedure (n =50). Scr, Ccr, blood β2-M, urine NAG/Cr, and urine osmolality before and after the procedure were compared between the groups. Results Baseline demographic characteristics and nephropathy risk factors were similar between groups. Cer was significantly reduced while blood β2-M and uric NAG/Cr were significantly increased in low dose group (all P ＜ 0.05) . Blood β2-M in the high dose group was significantly lower than that in the low dose group at day 1 [(2.35±0.52) mg/L vs. (2.67±0.64) mg/L, P =0.008], day 3[(2.49±0.55)mg/L vs. (2.80±0.64) mg/L,P =0.011] and day 5[(2.29±0.53) mg/L vs. (2.56±0.66) nag/L, P = 0.026] post-procedure respectively; urine NAG/Cr in the high dose group was also significantly lower than that in the low dose group at day 1 [(1.19±0.30) U/mmol vs. (1.46±0.34) U/mmol, P ＜ 0.001], day 3 [(1.30±0.30) U/mmol vs. (1.59±0.33) U/mmol, P ＜ 0.001], and day 5 [(1.10±0.30) U/mmol vs. (1.34±0.35) U/mmol, P = 0.001] post-procedure respectively;Cer in the high dose group was significantly higher than that in the low dose group at day 1 [(73.69±20.99) mL/min vs. (65.19±18.72) mL/min,P =0.035], day 3[(64.04±15.82) ml/min vs. (56.79±14.50)ml/min,P =0.019] post-procedure respectively. Conclusion High dose atorvastatin use before angiography is superior than low dose atorvastatin on attenuating contrast induced renal dysfunction.     

大剂量阿托伐他汀预防对比剂肾病

Objective To compare the efficacy of high and low dose atorvastatin on preventing contrast induced nephropathy (CIN) in patients underwent diagnostic and therapeutic coronary intervention. Methods All patients received atorvastatin 10 mg/d on the basis of hydrated therapy (n =100) and high dose group received additional atorvastatin 80 nag at 12 to 24 hours before procedure (n =50). Scr, Ccr, blood β2-M, urine NAG/Cr, and urine osmolality before and after the procedure were compared between the groups. Results Baseline demographic characteristics and nephropathy risk factors were similar between groups. Cer was significantly reduced while blood β2-M and uric NAG/Cr were significantly increased in low dose group (all P ＜ 0.05) . Blood β2-M in the high dose group was significantly lower than that in the low dose group at day 1 [(2.35±0.52) mg/L vs. (2.67±0.64) mg/L, P =0.008], day 3[(2.49±0.55)mg/L vs. (2.80±0.64) mg/L,P =0.011] and day 5[(2.29±0.53) mg/L vs. (2.56±0.66) nag/L, P = 0.026] post-procedure respectively; urine NAG/Cr in the high dose group was also significantly lower than that in the low dose group at day 1 [(1.19±0.30) U/mmol vs. (1.46±0.34) U/mmol, P ＜ 0.001], day 3 [(1.30±0.30) U/mmol vs. (1.59±0.33) U/mmol, P ＜ 0.001], and day 5 [(1.10±0.30) U/mmol vs. (1.34±0.35) U/mmol, P = 0.001] post-procedure respectively;Cer in the high dose group was significantly higher than that in the low dose group at day 1 [(73.69±20.99) mL/min vs. (65.19±18.72) mL/min,P =0.035], day 3[(64.04±15.82) ml/min vs. (56.79±14.50)ml/min,P =0.019] post-procedure respectively. Conclusion High dose atorvastatin use before angiography is superior than low dose atorvastatin on attenuating contrast induced renal dysfunction.     

大剂量阿托伐他汀预防对比剂肾病

Objective To compare the efficacy of high and low dose atorvastatin on preventing contrast induced nephropathy (CIN) in patients underwent diagnostic and therapeutic coronary intervention. Methods All patients received atorvastatin 10 mg/d on the basis of hydrated therapy (n =100) and high dose group received additional atorvastatin 80 nag at 12 to 24 hours before procedure (n =50). Scr, Ccr, blood β2-M, urine NAG/Cr, and urine osmolality before and after the procedure were compared between the groups. Results Baseline demographic characteristics and nephropathy risk factors were similar between groups. Cer was significantly reduced while blood β2-M and uric NAG/Cr were significantly increased in low dose group (all P ＜ 0.05) . Blood β2-M in the high dose group was significantly lower than that in the low dose group at day 1 [(2.35±0.52) mg/L vs. (2.67±0.64) mg/L, P =0.008], day 3[(2.49±0.55)mg/L vs. (2.80±0.64) mg/L,P =0.011] and day 5[(2.29±0.53) mg/L vs. (2.56±0.66) nag/L, P = 0.026] post-procedure respectively; urine NAG/Cr in the high dose group was also significantly lower than that in the low dose group at day 1 [(1.19±0.30) U/mmol vs. (1.46±0.34) U/mmol, P ＜ 0.001], day 3 [(1.30±0.30) U/mmol vs. (1.59±0.33) U/mmol, P ＜ 0.001], and day 5 [(1.10±0.30) U/mmol vs. (1.34±0.35) U/mmol, P = 0.001] post-procedure respectively;Cer in the high dose group was significantly higher than that in the low dose group at day 1 [(73.69±20.99) mL/min vs. (65.19±18.72) mL/min,P =0.035], day 3[(64.04±15.82) ml/min vs. (56.79±14.50)ml/min,P =0.019] post-procedure respectively. Conclusion High dose atorvastatin use before angiography is superior than low dose atorvastatin on attenuating contrast induced renal dysfunction.     

大剂量阿托伐他汀预防对比剂肾病

Objective To compare the efficacy of high and low dose atorvastatin on preventing contrast induced nephropathy (CIN) in patients underwent diagnostic and therapeutic coronary intervention. Methods All patients received atorvastatin 10 mg/d on the basis of hydrated therapy (n =100) and high dose group received additional atorvastatin 80 nag at 12 to 24 hours before procedure (n =50). Scr, Ccr, blood β2-M, urine NAG/Cr, and urine osmolality before and after the procedure were compared between the groups. Results Baseline demographic characteristics and nephropathy risk factors were similar between groups. Cer was significantly reduced while blood β2-M and uric NAG/Cr were significantly increased in low dose group (all P ＜ 0.05) . Blood β2-M in the high dose group was significantly lower than that in the low dose group at day 1 [(2.35±0.52) mg/L vs. (2.67±0.64) mg/L, P =0.008], day 3[(2.49±0.55)mg/L vs. (2.80±0.64) mg/L,P =0.011] and day 5[(2.29±0.53) mg/L vs. (2.56±0.66) nag/L, P = 0.026] post-procedure respectively; urine NAG/Cr in the high dose group was also significantly lower than that in the low dose group at day 1 [(1.19±0.30) U/mmol vs. (1.46±0.34) U/mmol, P ＜ 0.001], day 3 [(1.30±0.30) U/mmol vs. (1.59±0.33) U/mmol, P ＜ 0.001], and day 5 [(1.10±0.30) U/mmol vs. (1.34±0.35) U/mmol, P = 0.001] post-procedure respectively;Cer in the high dose group was significantly higher than that in the low dose group at day 1 [(73.69±20.99) mL/min vs. (65.19±18.72) mL/min,P =0.035], day 3[(64.04±15.82) ml/min vs. (56.79±14.50)ml/min,P =0.019] post-procedure respectively. Conclusion High dose atorvastatin use before angiography is superior than low dose atorvastatin on attenuating contrast induced renal dysfunction.     

分子吸附再循环系统治疗急慢性肝功能衰竭的临床研究

目的 总结用分子吸附再循环系统(moleclular adsorbent recirculating system, MARS)治疗各类原因所致肝功能衰竭患者的经验。方法 回顾并随访分析25例次MARS人工肝治疗的疗效。结果 单次6h MARS治疗显著降低患者血清总胆红素[(618.51±200.68)mmol/L到(390.81±146.02)mmol/L, t=2.729,P＜O.01]、间接胆红素[(490.03±163.39)mmol/L到(303.28±113.06)mmol/L,t=2.516,P＜0.01]和血氨[(152.44±82.62)mmol/L到(84.84±13.30)mmol/L,t=2.174, P＜0.05] 水平;升高凝血酶原活动度(70.55±32.39到93.63±14.20,t=1.728,P＜0.05)。肝功能酶谱、血清蛋白质、肾功能、电解质、血常规和血气分析指标无显著变化。17例患者,治愈和好转13例,死亡4例,存活率76.5%。结论MARS人工肝是治疗肝功能衰竭患者安全、有效的辅助方法。     

L-精氨酸对低氧性肺动脉高压大鼠肺动脉平滑肌细胞凋亡的影响

目的 探讨L-精氨酸(L-Arg)对低氧性肺动脉高压大鼠不同节段肺动脉平滑肌细胞凋亡的影响。方法 将Wistar大鼠(n=19)随机分为对照组(n=7)、低氧组(n=6)及低氧 L-Arg组(n=6)。经右心导管法测定各组大鼠肺动脉压力和右室(RV)/左室 室间隔(LV S)比值,以分光光度法间接测定血浆一氧化氮(NO)含量,通过TUNEL法检测各组大鼠不同节段的肺动脉平滑肌细胞凋亡数目,并计算肺动脉平滑肌细胞凋亡数目与肺动脉平滑肌细胞数目比值。结果 低氧组大鼠肺动脉平均压(PAMP)显著高于对照组[(2.71±0.29)kPa vs(2.05±0.14)kPa,P<0.01],低氧 L-Arg组大鼠的PAMP显著低于低氧组[(2.23±0.18)kPa vs(2.71±0.29)kPa,P<0.05];低氧组大鼠RV/(LV S)比值显著高于对照组[(0.42±0.03)kPa vs(0.30±0.05)kPa,P<0.01],低氧 L-Arg组大鼠RV/(LV S)比值显著低于低氧组[(0.36±0.02)kPa vs(0.42±0.03)kPa,P<0.01];低氧组大鼠血浆NO含量明显低于对照组[(3.54±0.47)μmol/L vs(4.79±0.17)μmol/L,P<0.05],低氧 L-Arg组大鼠血浆NO含量显著高于低氧组[(5.21±0.26)μmol/L vs(3.54±0.47)μmol/L,P<0.01];低氧组大鼠与终末细支气管伴行的肺动脉和与呼吸细支气管伴行的肺动脉平滑肌细胞凋亡数目与平滑肌细胞数目比值明显低于对照组[(0.051±0.016     

高浓度葡萄糖对牛视网膜血管周细胞凋亡及凋亡调节基因表达的影响

目的 研究不同浓度葡萄糖培养条件对牛视网膜血管周细胞凋亡及凋亡调节基因Bel-2、Bax表达的影响,探讨Bcl-2、Bax对周细胞凋亡的调控.方法 在体外培养第3代近融合的视网膜血管周细胞中加入不同浓度的葡萄糖(5.5 mmol/L、15.0 mmol/L、25.0 mmol/L和35.0mmol/L)孵育6 d后,应用MTT方法检测高糖下牛视网膜周细胞增殖情况,TUNEL法特异性标记凋亡细胞,免疫组化染色法和RT-PCR测定Bcl-2、Bax基因的表达. 结果 周细胞在高浓度葡萄糖培养下,细胞增殖受抑制,呈现出典型的细胞凋亡特征,凋亡率分别为(28.4±0.8)%、(40.4±0.9)%与(50.2±0.6)%.高浓度葡萄糖培养呈剂量依赖性促周细胞凋亡(r=0.959,P＜0.01)和凋亡调节基因Bax的表达(蛋白水平r=0.966,P＜0.01;mNRA水平r=0.874,P＜0.01)及抑制凋亡调节基因Bcl-2的表达(蛋白水平r=-0.964,P＜0.01;mNRA水平r=-0.912,P＜0.01);周细胞的凋亡率与Bax/Bcl-2比率呈正相关(r=0.810,P＜0.01).结论 高浓度葡萄糖培养以剂量依赖的方式促进周细胞凋亡,Bcl-2、Bax基因表达的改变参与了细胞凋亡的调控.     

酰基化Ghrelin在体外拮抗巨噬细胞介导的炎症反应对胰岛β细胞功能影响的研究

目的 采用Transwell小室构建的小鼠胰岛细胞株MIN6和巨噬细胞株RAW264.7共培养系统,探讨酰基化Ghrelin能否保护胰岛β细胞免遭巨噬细胞介导的炎症损伤. 方法 实验分为单独RAW264.7巨噬细胞组、单独MIN6胰岛细胞组、共培养组和Ghrelin干预组.RT-PCR和Western blot 检测巨噬细胞上Toll样受体4(TLR4)和脂肪酸结合蛋白(A-FABP)的表达;ELISA检测细胞上清液IL-1β、TNF-α的浓度,以及葡萄糖刺激后MIN6细胞上清液的胰岛素浓度. 结果 (1)共培养系统中,巨噬细胞TLR4[mRNA及蛋白水平分别为(1.35±0.13),(0.93±0.03)],A-FABP[(1.99±0.10)vs(0.91±o.01)]的表达],细胞上清液IL-1β[(10.47±1.11) pg/ml]、TNF-α[(917.54±9.09) pg/ml]蛋白水平较单独RAW264.7巨噬细胞组高(P＜0.05);(2)高糖刺激下,共培养系统中胰岛β细胞的胰岛素分泌水平较单独MIN6胰岛细胞组低(P＜0.05);(3)与共培养组比较,酰基化Ghrelin干预后共培养,巨噬细胞TLR4表达水平和TNF-α均降低(P＜0.05),且呈剂量依赖性,但胰岛β细胞的胰岛素分泌水平与共培养组比较,差异无统计学意义(P＞0.05). 结论 巨噬细胞与胰岛β细胞共培养后,炎症通路活化,炎症因子释放,胰岛β细胞的胰岛素分泌功能受损;酰基化Ghrelin可剂量依赖性削弱巨噬细胞和胰岛β细胞共培养后炎症通路的活化和炎症因子的释放,但不能完全阻止胰岛β细胞胰岛素分泌功能的降低.     

棕榈酸对小鼠胰岛β细胞瘤MIN6细胞凋亡的影响及其机制探讨

目的观察棕榈酸对小鼠胰岛β细胞瘤MIN6细胞凋亡的影响,并探讨其作用机制。方法培养于含0.5 mM棕榈酸的培养基中的MIN6细胞为实验组,仅含5%BSA的培养基培养的MIN6细胞为对照组,采用流式细胞术和原位末端转移酶标记技术(TUNEL)检测两组MIN6细胞凋亡情况。实验组于培养12(实验1组)、24(实验2组)、36(实验3组)h后,对照组于培养36 h后,采用Western blot法检测MIN6细胞中的凋亡诱导因子(AIF)及survivin。构建survivin过表达载体并转染实验组细胞,36 h后,同前法检测转染及未转染survivin过表达载体的MIN6细胞在含棕榈酸培养基中的凋亡情况。结果培养36 h后实验组MIN6细胞凋亡率为30.27%±3.15%,明显高于对照组的4.61%±0.51%(P<0.01)。实验1、2、3组MIN6细胞核中的AIF的相对表达量高于对照组,sur-vivin相对表达量低于对照组(P均<0.05)。棕榈酸培养36 h后,转染survivin过表达载体的MIN6细胞凋亡率为11.6%±2.09%,低于未转染者的31.27%±2.97%(P<0.01)。结论棕榈酸可诱导小鼠胰岛β细胞瘤MIN6细胞凋亡,可能与下调survivin表达和激活AIF凋亡信号通路有关;survivin表达上调可抑制棕榈酸诱导的MIN6细胞凋亡。     

Visfatin inhibits pancreatic β-cell line MIN6 apoptosis via PI3K-Akt and MAPK-ERK1/2 signaling pathways

探讨内脂素对胰岛β细胞株MIN6细胞信号通路和棕榈酸诱导细胞凋亡的影响,并探讨其分子机制.人重组内脂素呈剂量和时间依赖性促进MIN6细胞细胞外信号调节激酶(ERK)1/2和蛋白激酶B(Akt)的磷酸化,抑制棕榈酸诱导的MIN6细胞凋亡(P<0.05或P<0.01).激活磷脂酰肌醇3激酶(PBK)-Akt和丝裂原活化蛋白激酶(MAPK)-ERK1/2信号通路是内脂素抑制MIN6细胞凋亡的分子机制之一.     

蛋白酶体抑制剂MG 132对诱导激活的肝星状细胞凋亡的影响

目的观察蛋白酶体抑制剂MG 132对诱导体外培养激活的肝星状细胞(HSC)凋亡的影响.方法大鼠肝星状细胞分离采用胶原酶原位灌注法,用流式细胞仪和琼脂糖凝胶电泳法检测MG 132对诱导激活的HSC凋亡的影响.结果1、2、3μmol/L MG132培养HSC 24 h后,细胞周期分析发现S期细胞减少,G2/M期细胞显著增加(P＜0.01),呈现一个剂量依赖性的关系;流式细胞术检测到明显的亚G1峰,各组的凋亡指数(%)分别是12.70±1.7、17.52±2.3、22.60±3.4,与对照组(1.9±0.6)相比,差异有显著性(P＜0.01);3 μmol/L MG 132作用12、24、36、48 h,凋亡指数(%)分别是16.43±2.2、22.60±2.7、29.80±1.7和36.30±1.4,与对照组相比,差异有显著性(P＜0.01),呈现一个时间依赖性的关系;琼脂糖凝胶电泳可以看到明显的DNA梯带的形成.结论MG 132能够诱导激活的HSC发生凋亡,且在发生凋亡之前有一个明显的G2/M期的阻滞.     

短期胰岛素强化治疗诱导初诊2型糖尿病患者血糖长期良好控制的临床试验

目的　探讨短期胰岛素强化治疗对改善 2型糖尿病患者的胰岛 β细胞功能和血糖控制的影响。　方法　采用自身前后对照 ,观察 2 2例新诊断 2型糖尿病患者接受 2周短期胰岛素泵治疗前后胰岛 β细胞对血糖刺激的胰岛素第一时相分泌的变化 ,探讨胰岛 β细胞功能及其影响因素和随访短期胰岛素强化治疗对 (不采用任何降糖药物 )长期血糖控制的影响。　结果　治疗 2周后 ,治疗前后静脉葡萄糖试验中胰岛素曲线下面积、胰岛素峰值、胰岛素峰值差值、胰岛素与血糖总量比值、胰岛素与血糖增量比值及HomaB指数明显升高 (P <0 .0 5 ) ;HomaA指数明显下降 (P <0 .0 5 )。治疗前后胰岛素峰值呈正相关 (r=0 .5 2 1,P =0 .0 13)。有 15例患者仅采用饮食控制 ,平均随访 6个月时糖化血红蛋白为 5 .97%± 0 .5 9% ,空腹血糖为 ( 6 .3± 1.1)mmol/L ,OGTT 2h血糖为 ( 7.8± 2 .4 )mmol/L ,空腹胰岛素为 ( 9±4 ) μU/ml,OGTT 2h胰岛素为 ( 2 0± 5 ) μU/ml。 　结论　短期强化胰岛素治疗可以显著恢复代表胰岛 β细胞功能的血糖刺激的胰岛素第一时相分泌 ,使患者的糖尿病回到 2型糖尿病自然病程的更早期阶段 ,部分患者不用任何药物 ,仅通过饮食控制就可获得良好的血糖水平     

内脂素激活PI3K-Akt和MAPK-ERK1/2信号通路抑制MIN6细胞凋亡

探讨内脂素对胰岛β细胞株MIN6细胞信号通路和棕榈酸诱导细胞凋亡的影响,并探讨其分子机制.人重组内脂素呈剂量和时间依赖性促进MIN6细胞细胞外信号调节激酶(ERK)1/2和蛋白激酶B(Akt)的磷酸化,抑制棕榈酸诱导的MIN6细胞凋亡(P<0.05或P<0.01).激活磷脂酰肌醇3激酶(PBK)-Akt和丝裂原活化蛋白激酶(MAPK)-ERK1/2信号通路是内脂素抑制MIN6细胞凋亡的分子机制之一.     

高血压病患者胰岛β细胞功能变化及雷米普利的影响

目的探讨高血压病患者胰岛 β细胞功能变化及雷米普利对胰岛 β细胞功能和胰岛素敏感性的影响。 方法　用酶联免疫吸附法检测 2 4例健康人及 44例高血压病患者血浆胰岛素原 (PI)、真胰岛素 (TI) ,用放免法测定免疫反应性胰岛素水平 (IRI) ;并利用上述指标计算胰岛 β细胞功能指数 (PI/IRI)和胰岛素敏感性指数 (ISI) ,观察 2 1例高血压病患者给予血管紧张素转换酶抑制剂 (ACEI)雷米普利治疗前后上述指标的变化。结果　 (1)高血压病组患者与对照组比较胰岛素原 (17.2± 8.2vs7.9± 2 .8pmol/L)和免疫反应性胰岛素浓度 (2 1.0± 12 .4vs 14± 7.8μU/ml)有显著性差异 (P分别为 <0 0 1、<0 0 5 ) ,胰岛β细胞功能指数 (0 81± 0 32vs 0 5 6± 0 17)亦有显著性差异 (P <0 0 5 ) ,而真胰岛素水平 (8.4± 4.0vs 7.4± 2 .4μU/ml)无显著性差异 (P >0 0 5 ) ;(2 ) 2 1例高血压病患者用雷米普利治疗后免疫反应性胰岛素 (2 1.9± 5 .1vs 14.9± 4.1μU/ml )和胰岛素原水平 (19.3± 8.0vs 12 .5± 8.2 pmol/L)有显著性下降(P分别为 <0 0 1、<0 0 5 ) ;胰岛 β细胞功能指数 (0 78± 0 31vs 0 5 4± 0 16 )显著性下降 (P <0 0 1) ,胰岛素敏感性指数 (- 4.4± 0 6vs - 3.5± 0 2 )显著性提高 (P <0