Abstract Objecitve To explore whether phosphoinositide specific phospholipase C (PLC) activation via G protein in vascular smooth muscle cells (VSMCs) is altered in spontaneously hypertensive rats (SHR). Met...Abstract Objecitve To explore whether phosphoinositide specific phospholipase C (PLC) activation via G protein in vascular smooth muscle cells (VSMCs) is altered in spontaneously hypertensive rats (SHR). Methods The VSMCs derived from aortae of SHR and Wistar Kyoto (WKY) rats were loaded for 48 hours with myo inositol. Inositol phosphate release was initiated by the addition of 10 5 mol/L norepinephrine in intact cells or by guanosine 5' 0 (3 thio tri sphosphate) (GTP gamma S) in permeabilized cells. In the meantime, growth arrested VSMCs were stimulated by 10% calf serum for 0, 30, 45, or 60 min, then gene expressions of Gq alpha subunit (G alph a q) were observed. Results There were no significant differences in inositol 1, 4,5 triphosphate (IP 3) level and expression of G alpha q mRNA between quiescent VSMCs from SHR and that from WKY. When stimulated by norepinephrine, IP 3 production increased transiently with a peak level at 10 s in VSMCs from WKY, and a rapid biphasic IP 3 response, which was significantly higher than that of WKY, in VSMCs from SHR had been observed. G proteins activated by GTP gamma S significantly raised IP 3 production in VSMCs from SHR compared to WKY (SHR vs WKY: 234.8%±29.2% vs 142.4%±12.0% of basal IP 3, P<0.05). In addition, the serum effect showed an significant increase in expression of G alpha q mRNA in VSMCs from SHR. Conclusions The hereditary factors are not the only variable regulating IP 3 metabolism and G alpha q gene expression. Influences of multi environmental factors such as vasoactive compounds, together with genetic predisposition, palys an important role in the highly sensitive response of IP 3 production and G alpha q gene over expression in SHR.展开更多
目的观察自发性高血压大鼠(SHR)心肌的血管紧张素转换酶(ACE)和ACE2的表达,以及依那普利干预的影响。方法将15只SHR随机分为:SHR对照组(n=7)和依那普利组(n=8),分别给予安慰剂、依那普利15 mg/(kg.d)灌胃干预4周。干预结束后处死大鼠,...目的观察自发性高血压大鼠(SHR)心肌的血管紧张素转换酶(ACE)和ACE2的表达,以及依那普利干预的影响。方法将15只SHR随机分为:SHR对照组(n=7)和依那普利组(n=8),分别给予安慰剂、依那普利15 mg/(kg.d)灌胃干预4周。干预结束后处死大鼠,分离左心室,行RT-PCR、Western blot检测。同步取10只WKY大鼠作为正常血压对照组。结果 SHR心肌ACE的mRNA和蛋白质的表达都显著高于WKY组(1.68±0.34 vs 0.33±0.12和1.21±0.14 vs 0.71±0.11,P<0.05),而ACE2的mRNA和蛋白质表达皆明显低于WKY组(0.50±0.15 vs1.16±0.24和0.71±0.24 vs 1.22±0.14,P<0.05)。依那普利明显降低ACE的mRNA和蛋白质表达(0.44±0.19 vs1.68±0.34,P<0.01;0.87±0.13 vs 1.21±0.14,P<0.05),提升ACE2的mRNA表达(1.77±0.49 vs 0.50±0.15,P<0.05),对ACE2的蛋白表达无明显影响。结论 SHR心肌ACE明显升高,ACE2显著降低;依那普利可能通过降低ACE、升高ACE2而降低血压。展开更多
Accumulating evidence suggests that the nucleus accumbens, which is involved in mechanisms of reward and addiction, plays a role in the pathogenesis of depression and in the action of anti-depressants. In the current ...Accumulating evidence suggests that the nucleus accumbens, which is involved in mechanisms of reward and addiction, plays a role in the pathogenesis of depression and in the action of anti-depressants. In the current study, intraperitoneal injection of nomifensine, a dopamine reuptake inhibitor, decreased depression-like behaviors in the Wistar Kyoto rat model of depression in the sucrose-preference and forced swim tests. Nomifensine also reduced membrane excitability in medium spiny neurons in the core of the nucleus accumbens in the childhood Wistar Kyoto rats as evaluated by electrophysiological recording. In addition, the expression of dopamine D2-like receptor mRNA was downregulated in the nucleus accumbens, striatum and hippocampus of nomifensine-treated childhood Wistar Kyoto rats. These experimental ifndings indicate that impaired inhibition of medium spiny neurons, mediated by dopamine D2-like receptors, may be involved in the formation of depression-like behavior in childhood Wistar Kyoto rats, and that nomifensine can alleviate depressive behaviors by reducing medium spiny neuron membrane excitability.展开更多
目的:利用18脱氧葡萄糖正电子发射断层扫描和计算机断层扫描(PET-CT)技术,探究针刺人迎穴对自发性高血压(SHR)大鼠脑功能区葡萄糖代谢的影响。方法:将30只SHR大鼠(BP≥140 mm Hg)测量血压后随机分为模型组、人迎组、非穴针灸组,每组10只...目的:利用18脱氧葡萄糖正电子发射断层扫描和计算机断层扫描(PET-CT)技术,探究针刺人迎穴对自发性高血压(SHR)大鼠脑功能区葡萄糖代谢的影响。方法:将30只SHR大鼠(BP≥140 mm Hg)测量血压后随机分为模型组、人迎组、非穴针灸组,每组10只;以10只同等体质量的WKY大鼠作为对照组。人迎组和非穴针灸组针刺30 min,模型组和对照组不进行干预,然后使用PET-CT扫描采集大鼠脑功能图像,得到的图像用SPM8处理。结果:与模型组比较,人迎组大鼠被灭活的脑区有小脑、初级视觉皮层、次级视觉皮质和穹窿下器官等部位;被激活的脑区有嗅球、小脑、第Ⅳ脑室、蓝斑核、前庭内侧核、下丘脑外侧核。针刺人迎穴对于提升大脑葡萄糖代谢的作用比非穴针灸更明显。结论:针刺人迎穴能显著降低SHR的血压,针刺人迎穴并不是特异性的激活特定脑区,而是对SHR病理状态下正负激活的多个脑区发挥双向良性调节作用。展开更多
文摘Abstract Objecitve To explore whether phosphoinositide specific phospholipase C (PLC) activation via G protein in vascular smooth muscle cells (VSMCs) is altered in spontaneously hypertensive rats (SHR). Methods The VSMCs derived from aortae of SHR and Wistar Kyoto (WKY) rats were loaded for 48 hours with myo inositol. Inositol phosphate release was initiated by the addition of 10 5 mol/L norepinephrine in intact cells or by guanosine 5' 0 (3 thio tri sphosphate) (GTP gamma S) in permeabilized cells. In the meantime, growth arrested VSMCs were stimulated by 10% calf serum for 0, 30, 45, or 60 min, then gene expressions of Gq alpha subunit (G alph a q) were observed. Results There were no significant differences in inositol 1, 4,5 triphosphate (IP 3) level and expression of G alpha q mRNA between quiescent VSMCs from SHR and that from WKY. When stimulated by norepinephrine, IP 3 production increased transiently with a peak level at 10 s in VSMCs from WKY, and a rapid biphasic IP 3 response, which was significantly higher than that of WKY, in VSMCs from SHR had been observed. G proteins activated by GTP gamma S significantly raised IP 3 production in VSMCs from SHR compared to WKY (SHR vs WKY: 234.8%±29.2% vs 142.4%±12.0% of basal IP 3, P<0.05). In addition, the serum effect showed an significant increase in expression of G alpha q mRNA in VSMCs from SHR. Conclusions The hereditary factors are not the only variable regulating IP 3 metabolism and G alpha q gene expression. Influences of multi environmental factors such as vasoactive compounds, together with genetic predisposition, palys an important role in the highly sensitive response of IP 3 production and G alpha q gene over expression in SHR.
文摘目的观察自发性高血压大鼠(SHR)心肌的血管紧张素转换酶(ACE)和ACE2的表达,以及依那普利干预的影响。方法将15只SHR随机分为:SHR对照组(n=7)和依那普利组(n=8),分别给予安慰剂、依那普利15 mg/(kg.d)灌胃干预4周。干预结束后处死大鼠,分离左心室,行RT-PCR、Western blot检测。同步取10只WKY大鼠作为正常血压对照组。结果 SHR心肌ACE的mRNA和蛋白质的表达都显著高于WKY组(1.68±0.34 vs 0.33±0.12和1.21±0.14 vs 0.71±0.11,P<0.05),而ACE2的mRNA和蛋白质表达皆明显低于WKY组(0.50±0.15 vs1.16±0.24和0.71±0.24 vs 1.22±0.14,P<0.05)。依那普利明显降低ACE的mRNA和蛋白质表达(0.44±0.19 vs1.68±0.34,P<0.01;0.87±0.13 vs 1.21±0.14,P<0.05),提升ACE2的mRNA表达(1.77±0.49 vs 0.50±0.15,P<0.05),对ACE2的蛋白表达无明显影响。结论 SHR心肌ACE明显升高,ACE2显著降低;依那普利可能通过降低ACE、升高ACE2而降低血压。
基金supported by the National Natural Science Foundation of China,No.31271198 and 81121001grants from the Shanghai Committee of Science and Technology,No.11ZR1415900the State Key Laboratory of Medical Neurobiology,Fudan University,No.10-12
文摘Accumulating evidence suggests that the nucleus accumbens, which is involved in mechanisms of reward and addiction, plays a role in the pathogenesis of depression and in the action of anti-depressants. In the current study, intraperitoneal injection of nomifensine, a dopamine reuptake inhibitor, decreased depression-like behaviors in the Wistar Kyoto rat model of depression in the sucrose-preference and forced swim tests. Nomifensine also reduced membrane excitability in medium spiny neurons in the core of the nucleus accumbens in the childhood Wistar Kyoto rats as evaluated by electrophysiological recording. In addition, the expression of dopamine D2-like receptor mRNA was downregulated in the nucleus accumbens, striatum and hippocampus of nomifensine-treated childhood Wistar Kyoto rats. These experimental ifndings indicate that impaired inhibition of medium spiny neurons, mediated by dopamine D2-like receptors, may be involved in the formation of depression-like behavior in childhood Wistar Kyoto rats, and that nomifensine can alleviate depressive behaviors by reducing medium spiny neuron membrane excitability.
文摘目的:利用18脱氧葡萄糖正电子发射断层扫描和计算机断层扫描(PET-CT)技术,探究针刺人迎穴对自发性高血压(SHR)大鼠脑功能区葡萄糖代谢的影响。方法:将30只SHR大鼠(BP≥140 mm Hg)测量血压后随机分为模型组、人迎组、非穴针灸组,每组10只;以10只同等体质量的WKY大鼠作为对照组。人迎组和非穴针灸组针刺30 min,模型组和对照组不进行干预,然后使用PET-CT扫描采集大鼠脑功能图像,得到的图像用SPM8处理。结果:与模型组比较,人迎组大鼠被灭活的脑区有小脑、初级视觉皮层、次级视觉皮质和穹窿下器官等部位;被激活的脑区有嗅球、小脑、第Ⅳ脑室、蓝斑核、前庭内侧核、下丘脑外侧核。针刺人迎穴对于提升大脑葡萄糖代谢的作用比非穴针灸更明显。结论:针刺人迎穴能显著降低SHR的血压,针刺人迎穴并不是特异性的激活特定脑区,而是对SHR病理状态下正负激活的多个脑区发挥双向良性调节作用。
