AIM: To elucidate the mechanisms of mesenteric vasodilation in portal hypertension (PHT), with a focus on endothelin signaling. METHODS: PHT was induced in rats by common bile duct ligation (CBDL). Portal pressure (PP...AIM: To elucidate the mechanisms of mesenteric vasodilation in portal hypertension (PHT), with a focus on endothelin signaling. METHODS: PHT was induced in rats by common bile duct ligation (CBDL). Portal pressure (PP) was measured directly via catheters placed in the portal vein tract. The level of endothelin-1 (ET-1) in the mesenteric circulation was determined by radioimmunoassay, and the expression of the endothelin A receptor (ETAR) and endothelin B receptor (ETBR) was assessed by immunofluorescence and Western blot. Additionally, expression of G protein coupled kinase-2 (GRK2) and β-arrestin 2, which influence endothelin receptor sensitivity, were also studied by Western blot. RESULTS: PP of CBDL rats increased significantly (11.89 ± 1.38 mmHg vs 16.34 ± 1.63 mmHg). ET-1 expression decreased in the mesenteric circulation 2 and 4 wk after CBDL. ET-1 levels in the systemic circulation of CBDL rats were increased at 2 wk and decreased at 4 wk. There was no change in ETAR expression in response to CBDL; however, increased expression of ETBR in the endothelial cells of mesenteric arterioles and capillaries was observed. In sham-operated rats, ETBR was mainly expressed in the CD31+ endothelial cells of the arterioles. With development of PHT, in addition to the endothelial cells, ETBR expression was noticeably detectable in the SMA+ smooth muscle cells of arterioles and in the CD31+ capillaries. Following CBDL, increased expression of GRK2 was also found in mesenteric tissue, though there was no change in the level of β-arrestin 2. CONCLUSION: Decreased levels of ET-1 and increased ETBR expression in the mesenteric circulation following CBDL in rats may underlie mesenteric vasodilation in individuals with PHT. Mechanistically, increased GRK2 expression may lead to desensitization of ETAR, as well as other vasoconstrictors, promoting this vasodilatory effect.展开更多
AIM： To develop a pharmacodynamic model of porta hypertension from chronic hepatitis. METHODS： Pathological changes and collagen depositions were analyzed using morphometry to confirm CCI4-induced chronic hepatitis....AIM： To develop a pharmacodynamic model of porta hypertension from chronic hepatitis. METHODS： Pathological changes and collagen depositions were analyzed using morphometry to confirm CCI4-induced chronic hepatitis. At do, d28, ds6 and d84 of the process, the portal perfused velocities （μL/min） in isolated rat livers were exactly controlled with a quanti-fied pump. The pressure （mmHg） was monitored with a Physiological System. The geometric concentrations of phenylephrine or acetylcholine were added to a fixed volume （300 mL） of the circulating perfusate. The equation, the median effective concentration and its 95% confidence intervals of phenylephrine or acetyl- choline were regressed with Prism-4 software in non-linear fit and various slopes. In the isolated perfused rat livers with chronic hepatitis, both median effective concentrations were defined as the pharmacodynamic model of portal hypertension.CONCLUSION： A pharmacodynamic model of portal hypertension in isolated perfused rat livers with chronic hepatitis was defined as the median effective concen- trations of phenylephrine and acetylcholine.展开更多
The tribological properties and thermal-stress behaviors of C/C-SiC composites during braking were investigated aiming to simulate braking tests of high-speed trains. The temperature and structural fields of C/C-SiC c...The tribological properties and thermal-stress behaviors of C/C-SiC composites during braking were investigated aiming to simulate braking tests of high-speed trains. The temperature and structural fields of C/C-SiC composites during braking were fully coupled and simulated with ANSYS software. The results of tribological tests indicated that the C/C-SiC composites showed excellent static friction coefficient (0.68) and dynamic friction coefficient (average value of 0.36). The highest temperature on friction surface was 445℃. The simulated temperature field showed that the highest temperature which appeared on the friction surface during braking was about 463℃. Analysis regarding thermal-stress field showed that the highest thermal-stress on friction surface was 11.5 MPa. The temperature and thermal-stress distributions on friction surface during braking showed the same tendency.展开更多
The Chinese herbal formula Tongluo fiunao, containing the active components Panax notogin- seng and Gardenia jasminoides, has recently been patented and is in use clinically. It is known to be neuroprotective in cereb...The Chinese herbal formula Tongluo fiunao, containing the active components Panax notogin- seng and Gardenia jasminoides, has recently been patented and is in use clinically. It is known to be neuroprotective in cerebral ischemia, but the underlying pathway remains poorly understood. In the present study, we established a rat model of cerebral ischemia by occlusion of the middle cerebral artery, and administered Tongluo Jiunao, a positive control （Xuesai Tong, containing Panax notoginseng） or saline intraperitoneally to investigate the pathway involved in the action of TongIuo fiunao injection. 2,3,5-Triphenyltetrazolium chloride （TTC） staining showed that the cerebral infarct area was significantly smaller in model rats that received Tongluo fiunao than in those that received saline. Enzyme-linked immunosorbent assay revealed significantly greater expression of neurotrophin 3 and growth-associated protein 43 in ischemic cerebral tissue, and serum levels of neurotrophin 3, in the Tongluo Jiunao group than in the saline group. The reverse transcription polymerase chain reaction and immunohistochemical staining showed that after treatment with Tongluo fiunao or Xuesai Tong, tropomyosin-related kinase C gene expression and immunoreactivity were significantly elevated compared with saline, with the greatest expression observed after Tongluo Jiunao treatment. These findings suggest that Tongluo Jiunao injection exerts a neuroprotective effect in rats with cerebral ischemia by activating the neurotrophin 3/ tropomyosin-related kinase C pathway.展开更多
基金Supported by Grant from National Key New Drug Creation Project of China, No. 2009ZX09102
文摘AIM: To elucidate the mechanisms of mesenteric vasodilation in portal hypertension (PHT), with a focus on endothelin signaling. METHODS: PHT was induced in rats by common bile duct ligation (CBDL). Portal pressure (PP) was measured directly via catheters placed in the portal vein tract. The level of endothelin-1 (ET-1) in the mesenteric circulation was determined by radioimmunoassay, and the expression of the endothelin A receptor (ETAR) and endothelin B receptor (ETBR) was assessed by immunofluorescence and Western blot. Additionally, expression of G protein coupled kinase-2 (GRK2) and β-arrestin 2, which influence endothelin receptor sensitivity, were also studied by Western blot. RESULTS: PP of CBDL rats increased significantly (11.89 ± 1.38 mmHg vs 16.34 ± 1.63 mmHg). ET-1 expression decreased in the mesenteric circulation 2 and 4 wk after CBDL. ET-1 levels in the systemic circulation of CBDL rats were increased at 2 wk and decreased at 4 wk. There was no change in ETAR expression in response to CBDL; however, increased expression of ETBR in the endothelial cells of mesenteric arterioles and capillaries was observed. In sham-operated rats, ETBR was mainly expressed in the CD31+ endothelial cells of the arterioles. With development of PHT, in addition to the endothelial cells, ETBR expression was noticeably detectable in the SMA+ smooth muscle cells of arterioles and in the CD31+ capillaries. Following CBDL, increased expression of GRK2 was also found in mesenteric tissue, though there was no change in the level of β-arrestin 2. CONCLUSION: Decreased levels of ET-1 and increased ETBR expression in the mesenteric circulation following CBDL in rats may underlie mesenteric vasodilation in individuals with PHT. Mechanistically, increased GRK2 expression may lead to desensitization of ETAR, as well as other vasoconstrictors, promoting this vasodilatory effect.
基金Supported by The Major State Creative New Drug Project,No.2009ZX09502-017Education Ministry Science Foundation ofChina,No. 108019
文摘AIM： To develop a pharmacodynamic model of porta hypertension from chronic hepatitis. METHODS： Pathological changes and collagen depositions were analyzed using morphometry to confirm CCI4-induced chronic hepatitis. At do, d28, ds6 and d84 of the process, the portal perfused velocities （μL/min） in isolated rat livers were exactly controlled with a quanti-fied pump. The pressure （mmHg） was monitored with a Physiological System. The geometric concentrations of phenylephrine or acetylcholine were added to a fixed volume （300 mL） of the circulating perfusate. The equation, the median effective concentration and its 95% confidence intervals of phenylephrine or acetyl- choline were regressed with Prism-4 software in non-linear fit and various slopes. In the isolated perfused rat livers with chronic hepatitis, both median effective concentrations were defined as the pharmacodynamic model of portal hypertension.CONCLUSION： A pharmacodynamic model of portal hypertension in isolated perfused rat livers with chronic hepatitis was defined as the median effective concen- trations of phenylephrine and acetylcholine.
基金Project(51575536)supported by the National Natural Science Foundation of ChinaProject(2016YFB0301403)supported by the National Key Research and Development Program of ChinaProject(2017zzts435)supported by Graduate Degree Thesis Innovation Foundation of Central South University,China
文摘The tribological properties and thermal-stress behaviors of C/C-SiC composites during braking were investigated aiming to simulate braking tests of high-speed trains. The temperature and structural fields of C/C-SiC composites during braking were fully coupled and simulated with ANSYS software. The results of tribological tests indicated that the C/C-SiC composites showed excellent static friction coefficient (0.68) and dynamic friction coefficient (average value of 0.36). The highest temperature on friction surface was 445℃. The simulated temperature field showed that the highest temperature which appeared on the friction surface during braking was about 463℃. Analysis regarding thermal-stress field showed that the highest thermal-stress on friction surface was 11.5 MPa. The temperature and thermal-stress distributions on friction surface during braking showed the same tendency.
基金supported by grants from the National Basic Research Program(973 Program),No.2012CB518602the National Natural Science Foundation of China,No.30830120a grant from Beijing University of Chinese Medicine in China
文摘The Chinese herbal formula Tongluo fiunao, containing the active components Panax notogin- seng and Gardenia jasminoides, has recently been patented and is in use clinically. It is known to be neuroprotective in cerebral ischemia, but the underlying pathway remains poorly understood. In the present study, we established a rat model of cerebral ischemia by occlusion of the middle cerebral artery, and administered Tongluo Jiunao, a positive control （Xuesai Tong, containing Panax notoginseng） or saline intraperitoneally to investigate the pathway involved in the action of TongIuo fiunao injection. 2,3,5-Triphenyltetrazolium chloride （TTC） staining showed that the cerebral infarct area was significantly smaller in model rats that received Tongluo fiunao than in those that received saline. Enzyme-linked immunosorbent assay revealed significantly greater expression of neurotrophin 3 and growth-associated protein 43 in ischemic cerebral tissue, and serum levels of neurotrophin 3, in the Tongluo Jiunao group than in the saline group. The reverse transcription polymerase chain reaction and immunohistochemical staining showed that after treatment with Tongluo fiunao or Xuesai Tong, tropomyosin-related kinase C gene expression and immunoreactivity were significantly elevated compared with saline, with the greatest expression observed after Tongluo Jiunao treatment. These findings suggest that Tongluo Jiunao injection exerts a neuroprotective effect in rats with cerebral ischemia by activating the neurotrophin 3/ tropomyosin-related kinase C pathway.
