AIM: To assess the effect of notoginsenoside R1 on hepatic microcirculatory disturbance induced by gut ischemia/reperfusion (I/R) in mice. METHODS: The superior mesenteric artery (SMA) of C57/BL mice was ligated...AIM: To assess the effect of notoginsenoside R1 on hepatic microcirculatory disturbance induced by gut ischemia/reperfusion (I/R) in mice. METHODS: The superior mesenteric artery (SMA) of C57/BL mice was ligated for 15 min to induce gut ischemia followed by 30-rain reperfusion. In another set of experiments, R1 was continuously infused (10 mg/kg per hour) from 10 min before I/R until the end of the investigation to study the influence of R1 on hepatic microcirculatory disturbance induced by gut I/R. Hepatic microcirculation was observed by inverted microscopy, and the vascular diameter, red blood cell (RBC) velocity and sinusoid perfusion were estimated. Leukocyte rolling and adhesion were observed under a laser confocal microscope. Thirty and 60 min after reperfusion, lactate dehydrogenase (LDH), alanine aminotransferase (ALl') and aspartate transaminase (AST) in peripheral blood were determined. The expression of adhesion molecules CD11b/CD18 in neutrophils and tumor necrosis factor- alpha (TNF-α), interleukin-6 (IL-6) and monocyte chemotactic protein-1 (MCP-1) in plasma were evaluated by flow Oltometry. E-selectin and intercellular adhesion molecule-1 (ICAM-1) in hepatic tissue were examined by immunofluorescence.RESULTS: After gut I/R, the diameters of terminal portal venules and central veins, RBC velocity and the number of perfused sinusoids were decreased, while the leukocyte rolling and adhesion, the expression of E-selectin in hepatic vessels and CD18 in neutrophils, IL-6, MCP-1, LDH, ALT and AST were increased. R1 treatment attenuated these alterations except for IL-6 and MCP-1. CONCLUSION: R1 prevents I/R-induced hepatic microcirculation disturbance and hepatocyte injury, The effect of R1 is related to its inhibition of leukocyte rolling and adhesion by inhibiting the expression of E-selectin in endothelium and CD18 in neutrophils.展开更多
Objectives: To investigate the intestinal microflora status related to ischemia/reperfusion (I/R) liver injury and explore the possible mechanism. Methods: Specific pathogen free grade Sprague-Dawley rats were randomi...Objectives: To investigate the intestinal microflora status related to ischemia/reperfusion (I/R) liver injury and explore the possible mechanism. Methods: Specific pathogen free grade Sprague-Dawley rats were randomized into three groups: Control group (n=8), sham group (n=6) and I/R group (n=10). Rats in the control group did not receive any treatment, rats in the I/R group were subjected to 20 min of liver ischemia, and rats in the sham group were only subjected to sham operation. Twenty-two hours later, the rats were sacrificed and liver enzymes and malondialdehyde (MDA), superoxide dismutase (SOD), serum endotoxin,intestinal bacterial counts, intestinal mucosal histology, bacterial translocation to mesenteric lymph nodes, liver, spleen, and kidney were studied. Results: Ischemia/reperfusion increased liver enzymes, MDA, decreased SOD, and was associated with plasma endotoxin elevation in the I/R group campared to those in the sham group. Intestinal Bifidobacteria and Lactobacilli decreased and intestinal Enterobacterium and Enterococcus, bacterial translocation to kidney increased in the I/R group compared to the sham group. Intestinal microvilli were lost, disrupted and the interspace between cells became wider in the I/R group.Conclusion: I/R liver injury may lead to disturbance of intestinal microflora and impairment of intestinal mucosal barrier function,which contributes to endotoxemia and bacterial translocation to kidney.展开更多
Testicular torsion (TT) is a serious urologic emergency that is observed in adolescent males and that can lead to infertility if left untreated. The ischemia-reperfusion (I/R) injury due to TT has been implicated ...Testicular torsion (TT) is a serious urologic emergency that is observed in adolescent males and that can lead to infertility if left untreated. The ischemia-reperfusion (I/R) injury due to TT has been implicated in the pathogenesis of testicular damage. We investigated the effects of melatonin on oxidative damage in the ipsUateral and contralateral testes of rats induced by unilateral TT. A total of 21 prepubertal male Wistar albino rats were divided into three groups, each consisting of seven rats, In Group 1 (SHAM group): a sham operation to the left testis and bilateral orchiectomy were performed. In Group 2 (I/R group): I/R injury was created by rotating the left testis 720° in a clockwise direction for 2 h and detorsing the testis after 2 h. Group 3 (I/R + MEL group): rats were subjected to I/R injury and one-shot melatonin injection (50mgkg-1, intraperitoneal (i.p.)). The testes of the rats were excised bilaterally in all groups. The testicular tissue activities of antioxidant catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase enzymes (GSH-Px), and the tissue levels of malondialdehyde (MDA), protein carbonyl (PC) and nitric oxide (NO) were determined. Administration of melatonin caused a significant decrease in lipid peroxidation and enzyme activities in the ipsilateral testis when compared with the control group (P 〈 0.05). All of the changes in the enzyme activities of the contralateral testis were insignificant (P 〉 0.05). MDA levels were significantly altered in the contralateral testis (P = 0.009), Melatonin administration decreased the deleterious effects of I/R injury in the ipsilateral torted testes of the rats. The contralateral testes were slightly affected by unilateral TT.展开更多
Ng R, the receptor for the neurite outgrowth inhibitor Nogo-66, plays a critical role in the plasticity and regeneration of the nervous system after injury such as ischemic stroke. In the present study, we used immuno...Ng R, the receptor for the neurite outgrowth inhibitor Nogo-66, plays a critical role in the plasticity and regeneration of the nervous system after injury such as ischemic stroke. In the present study, we used immunohistochemistry to investigate the regional expression of Ng R in rat brain following middle cerebral artery occlusion(MCAO). Ng R protein expression was not observed in the center of the lesion, but was elevated in the marginal zone compared with control and sham-operated rats. The cerebral cortex and hippocampus(CA1, CA2, and CA3) showed the greatest expression of Ng R. Furthermore, Ng R expression was higher in the ipsilesional hemisphere than on the control side in the same coronal section. Although time-dependent changes in Ng R expression across brain regions had their own characteristics, the overall trend complied with the following rules: Ng R expression changes with time showed two peaks and one trough; the first peak in expression appeared between 1 and 3 days after MCAO; expression declined at 5 days; and the second peak occurred at 28 days.展开更多
Renal ischemia reperfusion injury increases renal generation of angiotensin II (Ang Ⅱ) which could wors- en renal vasocontraction. Thus, we investigated the hypothesis that renal ischemia reperfusion injury alters ...Renal ischemia reperfusion injury increases renal generation of angiotensin II (Ang Ⅱ) which could wors- en renal vasocontraction. Thus, we investigated the hypothesis that renal ischemia reperfusion injury alters renal af- ferent arteriolar responses to Ang II via production of hydrogen peroxide ( H202 ), or superoxide ( O2 ) or via al- tered angiotensin type 1 receptor (AT1R) expression. Afferent arterioles of mouse kidneys 24h after renal ischemia repeffusion or sham procedures were isolated and perfused. Responses to Ang II or norepinephrine (NE) were as- sessed by measurement of arteriolar luminal diameter. The mRNA expressions of AT1 receptor ( AT1 R) and AT2 re- ceptor (ATzR) were evaluated by quantificational real-time polymerase chain reaction. Compared to sham group, afferent arterioles from mouse kidneys after renal ischemia reperfusion had impaired contractions to Ang II ( -4.63 ± 3.06) % versus ( - 29.95 ± 1.31 ) % at 10 -9 tool · ^-1, p 〈 0.05 , ( - 27.07 ± 1 50) % versus ( - 41 74 ± 0.60) % at 10^-7 tool · L^-1, P 〈 0.05 ) that were normalized by incubation with PEG-catalase , but unaffected by PEG-SOD. However, the NE responses of afferent arterioles after renal ischemia reperfusion were unchanged. Com- pared to the sham group, renal ischemia reperfusion significantly increased the renal cortical H202 (0. 123 ± -1 0. 006) versus (0. 087 ± 0. 003) mmol·mg protein, P 〈 0.01 ), reduced catalase activity [ ( 14.81 ± 3.22) ver- sus (28.49 ± 1.62) units · mg^-1 protein, P 〈 0.01 ] and downregulated mRNA for AT1R (0.27 ± 0.02 versus 0.95 ± 0.02, P 〈 0.01 ). We conclude that afferent arteriolar responses to Ang II are impaired selectively in mice after renal ischemia reperfusion by accumulation of H202 and reduced expression of AT1R.展开更多
目的:观察首乌丹参方(Gold Theragran Salvia Mihiorrhiza Prescription,GTSMP)对大鼠缺血再灌注损伤心肌梗死范围及血中白介素-1β(IL-1β)、肿瘤坏死因子(TNF-α)的影响。方法:实验共设7个组:假手术组、缺血再灌注组(L/R...目的:观察首乌丹参方(Gold Theragran Salvia Mihiorrhiza Prescription,GTSMP)对大鼠缺血再灌注损伤心肌梗死范围及血中白介素-1β(IL-1β)、肿瘤坏死因子(TNF-α)的影响。方法:实验共设7个组:假手术组、缺血再灌注组(L/R组)和首乌丹参方高、中、低剂量组,对照药组(复方丹参滴丸、消心痛)。采用结扎大鼠冠状动脉前降支30min/开放120min建立心肌缺血再灌注损伤(L/R)模型,通过首乌丹参方预处理,观察L/R大鼠心肌梗死范围以及血中的IL-1β、TNF-α含量的变化。结果:首乌丹参方高、中两个剂量组梗塞程度明显减轻,梗塞区重占全心脏及左心室的百分比与模型组比较均有显著性差异(P〈0.01.0.001),以首乌丹参方中剂量组为优;首乌丹参方给药后血中TNF-α、IL-1β有不同程度的下降,其中以高、中剂量组为优(P〈0.01)。结论:首乌丹参方能够减轻TNF-α、IL-1β对缺血再灌注心肌的损伤。展开更多
基金Supported by Tianjin Tasly Group, Tianjin, China
文摘AIM: To assess the effect of notoginsenoside R1 on hepatic microcirculatory disturbance induced by gut ischemia/reperfusion (I/R) in mice. METHODS: The superior mesenteric artery (SMA) of C57/BL mice was ligated for 15 min to induce gut ischemia followed by 30-rain reperfusion. In another set of experiments, R1 was continuously infused (10 mg/kg per hour) from 10 min before I/R until the end of the investigation to study the influence of R1 on hepatic microcirculatory disturbance induced by gut I/R. Hepatic microcirculation was observed by inverted microscopy, and the vascular diameter, red blood cell (RBC) velocity and sinusoid perfusion were estimated. Leukocyte rolling and adhesion were observed under a laser confocal microscope. Thirty and 60 min after reperfusion, lactate dehydrogenase (LDH), alanine aminotransferase (ALl') and aspartate transaminase (AST) in peripheral blood were determined. The expression of adhesion molecules CD11b/CD18 in neutrophils and tumor necrosis factor- alpha (TNF-α), interleukin-6 (IL-6) and monocyte chemotactic protein-1 (MCP-1) in plasma were evaluated by flow Oltometry. E-selectin and intercellular adhesion molecule-1 (ICAM-1) in hepatic tissue were examined by immunofluorescence.RESULTS: After gut I/R, the diameters of terminal portal venules and central veins, RBC velocity and the number of perfused sinusoids were decreased, while the leukocyte rolling and adhesion, the expression of E-selectin in hepatic vessels and CD18 in neutrophils, IL-6, MCP-1, LDH, ALT and AST were increased. R1 treatment attenuated these alterations except for IL-6 and MCP-1. CONCLUSION: R1 prevents I/R-induced hepatic microcirculation disturbance and hepatocyte injury, The effect of R1 is related to its inhibition of leukocyte rolling and adhesion by inhibiting the expression of E-selectin in endothelium and CD18 in neutrophils.
文摘Objectives: To investigate the intestinal microflora status related to ischemia/reperfusion (I/R) liver injury and explore the possible mechanism. Methods: Specific pathogen free grade Sprague-Dawley rats were randomized into three groups: Control group (n=8), sham group (n=6) and I/R group (n=10). Rats in the control group did not receive any treatment, rats in the I/R group were subjected to 20 min of liver ischemia, and rats in the sham group were only subjected to sham operation. Twenty-two hours later, the rats were sacrificed and liver enzymes and malondialdehyde (MDA), superoxide dismutase (SOD), serum endotoxin,intestinal bacterial counts, intestinal mucosal histology, bacterial translocation to mesenteric lymph nodes, liver, spleen, and kidney were studied. Results: Ischemia/reperfusion increased liver enzymes, MDA, decreased SOD, and was associated with plasma endotoxin elevation in the I/R group campared to those in the sham group. Intestinal Bifidobacteria and Lactobacilli decreased and intestinal Enterobacterium and Enterococcus, bacterial translocation to kidney increased in the I/R group compared to the sham group. Intestinal microvilli were lost, disrupted and the interspace between cells became wider in the I/R group.Conclusion: I/R liver injury may lead to disturbance of intestinal microflora and impairment of intestinal mucosal barrier function,which contributes to endotoxemia and bacterial translocation to kidney.
文摘Testicular torsion (TT) is a serious urologic emergency that is observed in adolescent males and that can lead to infertility if left untreated. The ischemia-reperfusion (I/R) injury due to TT has been implicated in the pathogenesis of testicular damage. We investigated the effects of melatonin on oxidative damage in the ipsUateral and contralateral testes of rats induced by unilateral TT. A total of 21 prepubertal male Wistar albino rats were divided into three groups, each consisting of seven rats, In Group 1 (SHAM group): a sham operation to the left testis and bilateral orchiectomy were performed. In Group 2 (I/R group): I/R injury was created by rotating the left testis 720° in a clockwise direction for 2 h and detorsing the testis after 2 h. Group 3 (I/R + MEL group): rats were subjected to I/R injury and one-shot melatonin injection (50mgkg-1, intraperitoneal (i.p.)). The testes of the rats were excised bilaterally in all groups. The testicular tissue activities of antioxidant catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase enzymes (GSH-Px), and the tissue levels of malondialdehyde (MDA), protein carbonyl (PC) and nitric oxide (NO) were determined. Administration of melatonin caused a significant decrease in lipid peroxidation and enzyme activities in the ipsilateral testis when compared with the control group (P 〈 0.05). All of the changes in the enzyme activities of the contralateral testis were insignificant (P 〉 0.05). MDA levels were significantly altered in the contralateral testis (P = 0.009), Melatonin administration decreased the deleterious effects of I/R injury in the ipsilateral torted testes of the rats. The contralateral testes were slightly affected by unilateral TT.
基金supported by grants of the Guangdong Provincial Science and Technology Project in China,No.2013B022000098the Scientific Research Project of Guangzhou Medical University in China in 2014,No.2014C26
文摘Ng R, the receptor for the neurite outgrowth inhibitor Nogo-66, plays a critical role in the plasticity and regeneration of the nervous system after injury such as ischemic stroke. In the present study, we used immunohistochemistry to investigate the regional expression of Ng R in rat brain following middle cerebral artery occlusion(MCAO). Ng R protein expression was not observed in the center of the lesion, but was elevated in the marginal zone compared with control and sham-operated rats. The cerebral cortex and hippocampus(CA1, CA2, and CA3) showed the greatest expression of Ng R. Furthermore, Ng R expression was higher in the ipsilesional hemisphere than on the control side in the same coronal section. Although time-dependent changes in Ng R expression across brain regions had their own characteristics, the overall trend complied with the following rules: Ng R expression changes with time showed two peaks and one trough; the first peak in expression appeared between 1 and 3 days after MCAO; expression declined at 5 days; and the second peak occurred at 28 days.
文摘Renal ischemia reperfusion injury increases renal generation of angiotensin II (Ang Ⅱ) which could wors- en renal vasocontraction. Thus, we investigated the hypothesis that renal ischemia reperfusion injury alters renal af- ferent arteriolar responses to Ang II via production of hydrogen peroxide ( H202 ), or superoxide ( O2 ) or via al- tered angiotensin type 1 receptor (AT1R) expression. Afferent arterioles of mouse kidneys 24h after renal ischemia repeffusion or sham procedures were isolated and perfused. Responses to Ang II or norepinephrine (NE) were as- sessed by measurement of arteriolar luminal diameter. The mRNA expressions of AT1 receptor ( AT1 R) and AT2 re- ceptor (ATzR) were evaluated by quantificational real-time polymerase chain reaction. Compared to sham group, afferent arterioles from mouse kidneys after renal ischemia reperfusion had impaired contractions to Ang II ( -4.63 ± 3.06) % versus ( - 29.95 ± 1.31 ) % at 10 -9 tool · ^-1, p 〈 0.05 , ( - 27.07 ± 1 50) % versus ( - 41 74 ± 0.60) % at 10^-7 tool · L^-1, P 〈 0.05 ) that were normalized by incubation with PEG-catalase , but unaffected by PEG-SOD. However, the NE responses of afferent arterioles after renal ischemia reperfusion were unchanged. Com- pared to the sham group, renal ischemia reperfusion significantly increased the renal cortical H202 (0. 123 ± -1 0. 006) versus (0. 087 ± 0. 003) mmol·mg protein, P 〈 0.01 ), reduced catalase activity [ ( 14.81 ± 3.22) ver- sus (28.49 ± 1.62) units · mg^-1 protein, P 〈 0.01 ] and downregulated mRNA for AT1R (0.27 ± 0.02 versus 0.95 ± 0.02, P 〈 0.01 ). We conclude that afferent arteriolar responses to Ang II are impaired selectively in mice after renal ischemia reperfusion by accumulation of H202 and reduced expression of AT1R.
文摘目的:观察首乌丹参方(Gold Theragran Salvia Mihiorrhiza Prescription,GTSMP)对大鼠缺血再灌注损伤心肌梗死范围及血中白介素-1β(IL-1β)、肿瘤坏死因子(TNF-α)的影响。方法:实验共设7个组:假手术组、缺血再灌注组(L/R组)和首乌丹参方高、中、低剂量组,对照药组(复方丹参滴丸、消心痛)。采用结扎大鼠冠状动脉前降支30min/开放120min建立心肌缺血再灌注损伤(L/R)模型,通过首乌丹参方预处理,观察L/R大鼠心肌梗死范围以及血中的IL-1β、TNF-α含量的变化。结果:首乌丹参方高、中两个剂量组梗塞程度明显减轻,梗塞区重占全心脏及左心室的百分比与模型组比较均有显著性差异(P〈0.01.0.001),以首乌丹参方中剂量组为优;首乌丹参方给药后血中TNF-α、IL-1β有不同程度的下降,其中以高、中剂量组为优(P〈0.01)。结论:首乌丹参方能够减轻TNF-α、IL-1β对缺血再灌注心肌的损伤。