AIM： To delineate the mechanisms of renal vasoconstriction in hepatorenal syndrome （HRS）, we investigated the expression of type I inositol 1, 4, 5-triphosphate receptors （IP3R I） of kidney in mice with fulminant...AIM： To delineate the mechanisms of renal vasoconstriction in hepatorenal syndrome （HRS）, we investigated the expression of type I inositol 1, 4, 5-triphosphate receptors （IP3R I） of kidney in mice with fulminant hepatic failure （FHF）. METHODS： FHF was induced by lipopolysaccharide （LPS） in D-galactosamine （GAIN） sensitized BALB/c mice. There were 20 mice in normal saline （NS）-treated group, 20 mice in LPS-treated group, 20 mice in GaIN- treated group, and 60 mice in GalN/LPS-treated group （FHF group）. Liver and kidney tissues were obtained at 2, 6, and 9 h after administration. The liver and kidney specimens were stained with hematoxylin-eosin for studying morphological changes under light microscope. The expression of IP3R I in kidney tissue was tested by immunohistochemistry, Western blot and reverse transcription （RT）-PCR. RESULTS： Kidney tissues were morphologically normal at all time points in all groups. IP3R I proteins were found localized in the plasma region of glomerular mesangial cells （GMC） and vascular smooth muscle cells （VSMC） in kidney by immunohistochemical staining. In kidney of mice with FHF at 6 h and 9 h IP3R I staining was upregulated. Results from Western blot demonstrated consistent and significant increment of IP3R I expression in mice with FHF at 6 h and 9 h （t = 3.16, P 〈 0.05; t = 5.43, P 〈 0.01）. Furthermore, we evaluated IP3R I mRNA expression by RT-PCR and observed marked upregulation of IP3R I mRNA in FHF samples at 2 h, 6 h and 9 h compared to controls （t = 2.97, P 〈 0.05; t = 4.42, P 〈 0.01; t = 3.81, P 〈 0.01）. CONCLUSION： The expression of IP3R I protein increased in GMC and renal VSMC of mice with FHF, possibly caused by up-regulation of IP3R I mRNA.展开更多
AIM To detect the expression of typeⅠ inositol 1,4,5-trisphosphate receptor(IP3 RI) in the kidney of rats with hepatorenal syndrome(HRS).METHODS One hundred and twenty-five Sprague-Dawley rats were randomly divided i...AIM To detect the expression of typeⅠ inositol 1,4,5-trisphosphate receptor(IP3 RI) in the kidney of rats with hepatorenal syndrome(HRS).METHODS One hundred and twenty-five Sprague-Dawley rats were randomly divided into four groups to receive an intravenous injection of D-galactosamine(D-Gal N) plus lipopolysaccharide(LPS; group G/L, n = 50), D-Gal N alone(group G, n = 25), LPS alone(group L, n = 25), and normal saline(group NS, n = 25), respectively.At 3, 6, 9, 12, and 24 h after injection, blood, liver, and kidney samples were collected. Hematoxylineosin staining of liver tissue was performed to assess hepatocyte necrosis. Electron microscopy was used to observe ultrastructural changes in the kidney. Western blot analysis and real-time PCR were performed to detect the expression of IP3 RI protein and m RNA in the kidney, respectively.RESULTS Hepatocyte necrosis was aggravated gradually, which was most significant at 12 h after treatment with D-galactosamine/lipopolysaccharide, and was characterized by massive hepatocyte necrosis. At the same time, serum levels of biochemical indicators including liver and kidney function indexes were all significantly changed. The structure of the renal glomerulus and tubules was normal at all time points. Western blot analysis indicated that IP3 RI protein expression began to rise at 3 h(P < 0.05) and peaked at 12 h(P < 0.01). Real-time PCR demonstrated that IP3 RI m RNA expression began to rise at 3 h(P < 0.05) and peaked at 9 h(P < 0.01).CONCLUSION IP3 RI protein expression is increased in the kidney of HRS rats, and may be regulated at the transcriptional level.展开更多
目的探讨苯扎贝特干预后小鼠肝脏B族I型清道夫受体(SR-B1)m RNA变化及对小鼠体内胆固醇逆转运的影响。方法 28只C57BL/6小鼠随机分为4组,分别给予普通饲料、不同剂量的苯扎贝特(0.10%、0.25%、0.50%)添加普通饲料喂养4周后,腹腔注射经...目的探讨苯扎贝特干预后小鼠肝脏B族I型清道夫受体(SR-B1)m RNA变化及对小鼠体内胆固醇逆转运的影响。方法 28只C57BL/6小鼠随机分为4组,分别给予普通饲料、不同剂量的苯扎贝特(0.10%、0.25%、0.50%)添加普通饲料喂养4周后,腹腔注射经乙酰化低密度脂蛋白(ac-LDL)及3H-胆固醇处理过的小鼠巨噬细胞悬液(0.5 m L/鼠,细胞数达5.0×106),单独笼养24 h后取血,酶法测定血脂;测定血清、肝脏和粪便中的3H-胆固醇含量(占注射总量的百分比);逆转录聚合酶链反应测定小鼠肝脏SR-B1 m RNA表达。结果与对照组比较,苯扎贝特组小鼠肝脏SR-B1 m RNA表达水平增高,粪便中的胆固醇流出率增加。不同剂量苯扎贝特(0.10%、0.25%、0.50%)干预组血清3H-胆固醇含量较对照组显著增加,分别增加100%、131%和110%。不同剂量苯扎贝特(0.10%、0.25%、0.50%W/W)干预组小鼠肝脏3H-胆固醇含量较对照组显著增加,分别增加86.4%、52.3%和51.6%。不同剂量苯扎贝特(0.10%、0.25%、0.50%)干预组小鼠粪便3H-胆固醇含量较对照组显著增加,分别增加为110%、140%和160%。结论苯扎贝特能上调肝脏SR-B1 m RNA表达,促进体内胆固醇逆转运,加速胆固醇由粪便清除,利于动脉粥样硬化的防治。展开更多
基金Supported by National Natural Science Foundation of China, No. 30270607
文摘AIM： To delineate the mechanisms of renal vasoconstriction in hepatorenal syndrome （HRS）, we investigated the expression of type I inositol 1, 4, 5-triphosphate receptors （IP3R I） of kidney in mice with fulminant hepatic failure （FHF）. METHODS： FHF was induced by lipopolysaccharide （LPS） in D-galactosamine （GAIN） sensitized BALB/c mice. There were 20 mice in normal saline （NS）-treated group, 20 mice in LPS-treated group, 20 mice in GaIN- treated group, and 60 mice in GalN/LPS-treated group （FHF group）. Liver and kidney tissues were obtained at 2, 6, and 9 h after administration. The liver and kidney specimens were stained with hematoxylin-eosin for studying morphological changes under light microscope. The expression of IP3R I in kidney tissue was tested by immunohistochemistry, Western blot and reverse transcription （RT）-PCR. RESULTS： Kidney tissues were morphologically normal at all time points in all groups. IP3R I proteins were found localized in the plasma region of glomerular mesangial cells （GMC） and vascular smooth muscle cells （VSMC） in kidney by immunohistochemical staining. In kidney of mice with FHF at 6 h and 9 h IP3R I staining was upregulated. Results from Western blot demonstrated consistent and significant increment of IP3R I expression in mice with FHF at 6 h and 9 h （t = 3.16, P 〈 0.05; t = 5.43, P 〈 0.01）. Furthermore, we evaluated IP3R I mRNA expression by RT-PCR and observed marked upregulation of IP3R I mRNA in FHF samples at 2 h, 6 h and 9 h compared to controls （t = 2.97, P 〈 0.05; t = 4.42, P 〈 0.01; t = 3.81, P 〈 0.01）. CONCLUSION： The expression of IP3R I protein increased in GMC and renal VSMC of mice with FHF, possibly caused by up-regulation of IP3R I mRNA.
基金Supported by Natural Science Foundation of Liaoning Province,No.20170540826Science and Technology Program of Shenyang City,No.18-014-4-49Innovation Support Program of Shenyang City for Young and Middle-Aged Researchers,No.RC170051
文摘AIM To detect the expression of typeⅠ inositol 1,4,5-trisphosphate receptor(IP3 RI) in the kidney of rats with hepatorenal syndrome(HRS).METHODS One hundred and twenty-five Sprague-Dawley rats were randomly divided into four groups to receive an intravenous injection of D-galactosamine(D-Gal N) plus lipopolysaccharide(LPS; group G/L, n = 50), D-Gal N alone(group G, n = 25), LPS alone(group L, n = 25), and normal saline(group NS, n = 25), respectively.At 3, 6, 9, 12, and 24 h after injection, blood, liver, and kidney samples were collected. Hematoxylineosin staining of liver tissue was performed to assess hepatocyte necrosis. Electron microscopy was used to observe ultrastructural changes in the kidney. Western blot analysis and real-time PCR were performed to detect the expression of IP3 RI protein and m RNA in the kidney, respectively.RESULTS Hepatocyte necrosis was aggravated gradually, which was most significant at 12 h after treatment with D-galactosamine/lipopolysaccharide, and was characterized by massive hepatocyte necrosis. At the same time, serum levels of biochemical indicators including liver and kidney function indexes were all significantly changed. The structure of the renal glomerulus and tubules was normal at all time points. Western blot analysis indicated that IP3 RI protein expression began to rise at 3 h(P < 0.05) and peaked at 12 h(P < 0.01). Real-time PCR demonstrated that IP3 RI m RNA expression began to rise at 3 h(P < 0.05) and peaked at 9 h(P < 0.01).CONCLUSION IP3 RI protein expression is increased in the kidney of HRS rats, and may be regulated at the transcriptional level.
文摘目的探讨苯扎贝特干预后小鼠肝脏B族I型清道夫受体(SR-B1)m RNA变化及对小鼠体内胆固醇逆转运的影响。方法 28只C57BL/6小鼠随机分为4组,分别给予普通饲料、不同剂量的苯扎贝特(0.10%、0.25%、0.50%)添加普通饲料喂养4周后,腹腔注射经乙酰化低密度脂蛋白(ac-LDL)及3H-胆固醇处理过的小鼠巨噬细胞悬液(0.5 m L/鼠,细胞数达5.0×106),单独笼养24 h后取血,酶法测定血脂;测定血清、肝脏和粪便中的3H-胆固醇含量(占注射总量的百分比);逆转录聚合酶链反应测定小鼠肝脏SR-B1 m RNA表达。结果与对照组比较,苯扎贝特组小鼠肝脏SR-B1 m RNA表达水平增高,粪便中的胆固醇流出率增加。不同剂量苯扎贝特(0.10%、0.25%、0.50%)干预组血清3H-胆固醇含量较对照组显著增加,分别增加100%、131%和110%。不同剂量苯扎贝特(0.10%、0.25%、0.50%W/W)干预组小鼠肝脏3H-胆固醇含量较对照组显著增加,分别增加86.4%、52.3%和51.6%。不同剂量苯扎贝特(0.10%、0.25%、0.50%)干预组小鼠粪便3H-胆固醇含量较对照组显著增加,分别增加为110%、140%和160%。结论苯扎贝特能上调肝脏SR-B1 m RNA表达,促进体内胆固醇逆转运,加速胆固醇由粪便清除,利于动脉粥样硬化的防治。
