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
This study aimed to elucidate the molecular mechanisms by which berberine protects against cerebral ischemia/reperfusion(I/R)injury.The oxygen-glucose deprivation/reperfusion(OGD/R)PC12 model was established.Cell coun...This study aimed to elucidate the molecular mechanisms by which berberine protects against cerebral ischemia/reperfusion(I/R)injury.The oxygen-glucose deprivation/reperfusion(OGD/R)PC12 model was established.Cell counting kit-8(CCK-8)was used to detect the toxicity of berberine and the viability of PC12 cells.Hoechst 33258 staining and flow cytometry were used to observe the nuclear morphology,and changes of apoptosis and reactive oxygen species(ROS),respectively.Western blotting and immunofluorescence assay were employed to detect autophagy-related proteins[microtubule-associated protein 1A/1B-light chain 3(LC3),P62/SQSTM-1,Beclin-1]and endoplasmic reticulum(ER)stress-related markers[glucose-regulated protein 78(GRP78),C/EBP homologous protein(CHOP),Bcl-2-associated X(Bax)and cleaved caspase-3].The GFP-RFP-LC3 adenovirus was used to assay the change of autophagic flux.Our results showed that berberine could increase the viability of PC12 cells,decrease the concentrations of ROS after OGD/R treatment,and suppress OGD/R-induced ER stress and autophagy.Moreover,the results revealed the involvement of the mammalian target of rapamycin(mTOR)pathway in the induction of autophagy,and berberine could activate the phosphorylation of mTOR and thus mitigate autophagy.In conclusion,our study suggested that berberine may protect against OGD/R-induced apoptosis by regulating ER stress and autophagy,and it holds promises in the treatment of cerebral I/R injury.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
The effect of chronic ozone exposure to ischemia reperfusion (I/R) injury in isolated perfused rat hearts was previously demonstrated. The present study tested our hypothesis that chronic ozone exposure led to attenua...The effect of chronic ozone exposure to ischemia reperfusion (I/R) injury in isolated perfused rat hearts was previously demonstrated. The present study tested our hypothesis that chronic ozone exposure led to attenuation of polyamines in the heart, which may limit sensitivity to I/R. Sprague Dawley rats were continuously exposed for 8 hrs/day for 28 days to filtered air or 0.8 ppm ozone. Isolated hearts were previously subjected to 0.5 hour of global ischemia followed by 1 hour of reperfusion after which global polyamine content was examined between the two groups. Spermidine production was significantly increased in the experimental group compared to control group (of I/R hearts). These results suggest that ozone-induced sensitivity to chronic I/R injury activates myocardial polyamine stress response characterized by increased enzymatic activities and accumulation of spermidine. Collectively, these results suggest that I/R possibly disturbs polyamine metabolism, and increased oxidative stress and concomitant reduced myocardial cell viability.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.
基金This work was supported by grants from the National Natural Science Foundation of China(No.81360199)Science and Technology Department of Guizhou Province(Guizhou Specific Grant[2019]4008)+2 种基金Science and Technology Plan Project of Guizhou Province(Basic Science and Technology Cooperation[2020]1Z060)Science and Technology Fund Project of Guizhou Health and Health Commission(No.gzwjkj2019-1-039)Science and Technology Fund Project of Southwest Guizhou Autonomous Prefecture(2019-1-10).
文摘This study aimed to elucidate the molecular mechanisms by which berberine protects against cerebral ischemia/reperfusion(I/R)injury.The oxygen-glucose deprivation/reperfusion(OGD/R)PC12 model was established.Cell counting kit-8(CCK-8)was used to detect the toxicity of berberine and the viability of PC12 cells.Hoechst 33258 staining and flow cytometry were used to observe the nuclear morphology,and changes of apoptosis and reactive oxygen species(ROS),respectively.Western blotting and immunofluorescence assay were employed to detect autophagy-related proteins[microtubule-associated protein 1A/1B-light chain 3(LC3),P62/SQSTM-1,Beclin-1]and endoplasmic reticulum(ER)stress-related markers[glucose-regulated protein 78(GRP78),C/EBP homologous protein(CHOP),Bcl-2-associated X(Bax)and cleaved caspase-3].The GFP-RFP-LC3 adenovirus was used to assay the change of autophagic flux.Our results showed that berberine could increase the viability of PC12 cells,decrease the concentrations of ROS after OGD/R treatment,and suppress OGD/R-induced ER stress and autophagy.Moreover,the results revealed the involvement of the mammalian target of rapamycin(mTOR)pathway in the induction of autophagy,and berberine could activate the phosphorylation of mTOR and thus mitigate autophagy.In conclusion,our study suggested that berberine may protect against OGD/R-induced apoptosis by regulating ER stress and autophagy,and it holds promises in the treatment of cerebral I/R injury.
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.
文摘The effect of chronic ozone exposure to ischemia reperfusion (I/R) injury in isolated perfused rat hearts was previously demonstrated. The present study tested our hypothesis that chronic ozone exposure led to attenuation of polyamines in the heart, which may limit sensitivity to I/R. Sprague Dawley rats were continuously exposed for 8 hrs/day for 28 days to filtered air or 0.8 ppm ozone. Isolated hearts were previously subjected to 0.5 hour of global ischemia followed by 1 hour of reperfusion after which global polyamine content was examined between the two groups. Spermidine production was significantly increased in the experimental group compared to control group (of I/R hearts). These results suggest that ozone-induced sensitivity to chronic I/R injury activates myocardial polyamine stress response characterized by increased enzymatic activities and accumulation of spermidine. Collectively, these results suggest that I/R possibly disturbs polyamine metabolism, and increased oxidative stress and concomitant reduced myocardial cell viability.
