目的探讨炎症条件的动物输注贮存红细胞对巨噬细胞(BMDMs)的调节作用以及贮存红细胞输注与细菌感染引发炎症反应的关系。方法将6~8周龄成年雄性C57BL/6小鼠[(18~22)g/只]40只随机均分为实验组和实验对照组(对照组),均通过动物尾静脉注...目的探讨炎症条件的动物输注贮存红细胞对巨噬细胞(BMDMs)的调节作用以及贮存红细胞输注与细菌感染引发炎症反应的关系。方法将6~8周龄成年雄性C57BL/6小鼠[(18~22)g/只]40只随机均分为实验组和实验对照组(对照组),均通过动物尾静脉注射铜绿假单胞菌200μL/只,并使用吸入式麻醉剂异氟烷(1%~3%)麻醉后,通过小鼠眼后静脉丛,实验组输注鼠源贮存悬浮红细胞(>14 d)400μL/只、对照组每只输注等量新鲜悬浮红细胞(贮存<24 h);于输注后2、4、8 h脱就猝死各结束2组小鼠生命5只,摘取鼠肝,体外培养铜绿假单胞菌感染(200μL/只)小鼠的股骨、胫骨骨髓来源的BMDMs,流式细胞术检测BMDMs中分化簇86(CD86)、分化簇197(CD197)[巨噬细胞1型(M1)基因特异性标志物]、分化簇209(CD209)[巨噬细胞2型(M2)基因特异性标记]表达水平,实时荧光定量PCR(qRT-PCR)法检测小鼠肝脏F4/80、M1、M2基因表达水平,并使用SPSS17.0统计学软件分析数据。结果实验组与对照组BMDMs中CD86和CD197的表达(%)分别为8688±1.01 vs 79.24±2.65、38.59±3.73 vs 25.95±0.86(P<0.05),CD209(%)为23.88±2.23 vs 21.91±3.58(P>0.05)。输注红细胞后2、4 h,小鼠肝F4/80基因表达水平实验组和对照组分别为1.83±0.11 vs 0.75±0.06、0.46±0.06 vs 0.33±0.06(P<0.05),8 h后分别为0.33±0.03 vs 0.35±0.05(P>0.05);输注红细胞2、4、8 h,小鼠肝M1基因中诱导型一氧化氮合酶(iNOS)基因表达水平实验组和对照组分别为3.44±0.20 vs 2.46±0.08、9.25±0.55 vs 2.67±0.12、2.80±0.08 vs 2.39±0.01,肿瘤坏死因子-α(TNF-α)分别为1.69±0.22 vs 1.13±0.03、1.44±0.24 vs 0.96±0.09、1.31±0.05 vs 0.96±0.06,单核细胞趋化蛋白1(MCP1)分别为4.96±0.08 vs 4.28±0.27、4.63±0.04 vs 2.07±0.09、2.28±0.19 vs 1.33±0.03(P<0.05);M2基因中精氨酸1(Arg1)基因表达水平实验组和对照组分别为0.81±0.21 vs 0.82±0.18、0.66±0.11 vs 0.58±0.09、0.39±0.17 vs 0.37±0.15,甘露糖受体C型2(Mrc2)分别为0.99±0.91 vs 0.97±0.08、0.98±0.12 vs 1.02±0.11、0.59±0.19 vs 0.57±0.08,重组蛋白163(CD163)分别为1.75±0.20 vs 1.69±0.18、0.22±0.02 vs 0.21±0.01、0.04±0.01 vs 0.03±0.01(P>0.05)。结论实验小鼠输注贮存红细胞明显促进其肝脏组织巨噬细胞朝向M1表型的极化。展开更多
Most studies on spinal cord neuronal injury have focused on spinal cord tissue histology and the expression of nerve cell damage and repair-related genes. The importance of the microcirculation is often ignored in spi...Most studies on spinal cord neuronal injury have focused on spinal cord tissue histology and the expression of nerve cell damage and repair-related genes. The importance of the microcirculation is often ignored in spinal cord injury and repair research. Therefore, in this study, we established a rat model of intervertebral disc extrusion by inserting a silica gel pad into the left ventral sur-face of T13. Electroacupuncture was used to stimulate the bilateralZusanlipoint （ST36） and Neiting point （ST44） for 14 days. Compared with control animals, blood lfow in the ifrst lumbar vertebra （L1） was noticeably increased in rats given electroacupuncture. Microvessel density in the T13 segment of the spinal cord was increased significantly as well. The number of normal neurons was higher in the ventral horn of the spinal cord. In addition, vacuolation in the white matter was lessened. No obvious glial cell proliferation was visible. Furthermore, hindlimb motor function was improved signiifcantly. Collectively, our results suggest that electroacupuncture can improve neuronal morphology and microcirculation, and promote the recovery of neurological functions in a rat model of intervertebral disc extrusion.展开更多
Intestinal alkaline phosphatase(IAP) plays an essential role in intestinal homeostasis and health through interactions with the resident microbiota, diet and the gut. IAP's role in the intestine is to dephosphoryl...Intestinal alkaline phosphatase(IAP) plays an essential role in intestinal homeostasis and health through interactions with the resident microbiota, diet and the gut. IAP's role in the intestine is to dephosphorylate toxic microbial ligands such as lipopolysaccharides, unmethylated cytosine-guanosine dinucleotides and flagellin as well as extracellular nucleotides such as uridine diphosphate. IAP's ability to detoxify these ligands is essential in protecting the host from sepsis during acute inflammation and chronic inflammatory conditions such as inflammatory bowel disease. Also important in these complications is IAP's ability to regulate the microbial ecosystem by forming a complex relationship between microbiota, diet and the intestinal mucosal surface. Evidence reveals that diet alters IAP expression and activity and this in turn can influence the gut microbiota and homeostasis. IAP's ability to maintain a healthygastrointestinal tract has accelerated research on its potential use as a therapeutic agent against a multitude of diseases.Exogenous IAP has been shown to have beneficial effects when administered during ulcerative colitis,coronary bypass surgery and sepsis.There are currently a handful of human clinical trials underway investigating the effects of exogenous IAP during sepsis,rheumatoid arthritis and heart surgery.In light of these findings IAP has been marked as a novel agent to help treat a variety of other inflammatory and infectious diseases.The purpose of this review is to highlight the essential characteristics of IAP in protection and maintenance of intestinal homeostasis while addressing the intricate interplay between IAP,diet,microbiota and the intestinal epithelium.展开更多
Aim DL0805-2 is a novel Rho-kinases inhibitor which has been found to have potent cardiovascular effects. In the present research, we aimed to study the potential of DL0805-2 in the treatment of pulmonary arterial hyp...Aim DL0805-2 is a novel Rho-kinases inhibitor which has been found to have potent cardiovascular effects. In the present research, we aimed to study the potential of DL0805-2 in the treatment of pulmonary arterial hypertension （PAH） and discuss the underlying mechanisms preliminarily. Methods A classical PAH animal model was used, which was established by single injection of 50 mg · kg^-1 monocrotaline （MCT）. One week later, the rats were administrated with 1, 3, 10 mg · kg^-1 DL0805-2 via intraperitoneal injection for 18 days. At the end of the experiment, the body weight and survival rate were recorded. Meanwhile, the respiration function, heart function, blood pressure and pulmonary artery pressure were detected. Serum was collected for biochemical index analysis. The weight of vital organs was used to calculate the organ index. Histopathology examination was em-ployed to observe the subtle changes in hearts, vessels and lungs. Furthermore, the mechanisms were studied main- ly by the method of western blotting. Results DL0805-2 did not show significant influence on body weight of PAH rats. But the survival rate of PAH rats treated with 3 and 10 mg · kg^-1 DL0805-2 was increased up to 90. 9% com- pared with the model group （68.2%）. DL0805-2 improved the pulmonary artery blood flow especially the maximal -1 -1 velocity （PV max） from 397.2 cm · s^-1 to 506.5, 540. 1 and 574.0 cm · s^-1 respectively. The results of echocar- diography and electrocardiogram show that DL0805-2 had little effect on left ventricle and systemic circulation but attenuated right ventricle injury and decreased the right ventricle pressure from 73.73 mmHg to 47.80, 42.64 and 46.45 mmHg respectively after DL0805-2 intervention. Disease markers of PAH including NT-proBNP in serum and ET-1 in lung tissue homogenate and serum biochemical indicators, ALT, AST and LDH, were reduced by DL0805-2. DL0805-2 also relieved edema of lungs and decreased inflammatory cytokines production. Through the examination on histopathologic slide of pulmonary main artery, right ventricle and lung, DL0805 derivatives were found to have significant protection effect on structural changes of organs induced by pulmonary hypertension. Ac- cording to the preliminary study on the mechanisms of DL0805-2 in PAH, Rho/ROCK pathway was significantly in- hibited by DL0805 derivatives. In addition, DL0805 derivatives showed effect on BMPRII/p-Smad pathway and ap- optosis related pathway. Conclusion DL0805-2 has showed potent treatment effect on the PAH rats. And the un- derlying mechanisms studies also indicated that RhoA/ROCK and BMPRII pathways were involved. This work will provide basis experimental data for the further research and development of DL0805-2.展开更多
文摘目的探讨炎症条件的动物输注贮存红细胞对巨噬细胞(BMDMs)的调节作用以及贮存红细胞输注与细菌感染引发炎症反应的关系。方法将6~8周龄成年雄性C57BL/6小鼠[(18~22)g/只]40只随机均分为实验组和实验对照组(对照组),均通过动物尾静脉注射铜绿假单胞菌200μL/只,并使用吸入式麻醉剂异氟烷(1%~3%)麻醉后,通过小鼠眼后静脉丛,实验组输注鼠源贮存悬浮红细胞(>14 d)400μL/只、对照组每只输注等量新鲜悬浮红细胞(贮存<24 h);于输注后2、4、8 h脱就猝死各结束2组小鼠生命5只,摘取鼠肝,体外培养铜绿假单胞菌感染(200μL/只)小鼠的股骨、胫骨骨髓来源的BMDMs,流式细胞术检测BMDMs中分化簇86(CD86)、分化簇197(CD197)[巨噬细胞1型(M1)基因特异性标志物]、分化簇209(CD209)[巨噬细胞2型(M2)基因特异性标记]表达水平,实时荧光定量PCR(qRT-PCR)法检测小鼠肝脏F4/80、M1、M2基因表达水平,并使用SPSS17.0统计学软件分析数据。结果实验组与对照组BMDMs中CD86和CD197的表达(%)分别为8688±1.01 vs 79.24±2.65、38.59±3.73 vs 25.95±0.86(P<0.05),CD209(%)为23.88±2.23 vs 21.91±3.58(P>0.05)。输注红细胞后2、4 h,小鼠肝F4/80基因表达水平实验组和对照组分别为1.83±0.11 vs 0.75±0.06、0.46±0.06 vs 0.33±0.06(P<0.05),8 h后分别为0.33±0.03 vs 0.35±0.05(P>0.05);输注红细胞2、4、8 h,小鼠肝M1基因中诱导型一氧化氮合酶(iNOS)基因表达水平实验组和对照组分别为3.44±0.20 vs 2.46±0.08、9.25±0.55 vs 2.67±0.12、2.80±0.08 vs 2.39±0.01,肿瘤坏死因子-α(TNF-α)分别为1.69±0.22 vs 1.13±0.03、1.44±0.24 vs 0.96±0.09、1.31±0.05 vs 0.96±0.06,单核细胞趋化蛋白1(MCP1)分别为4.96±0.08 vs 4.28±0.27、4.63±0.04 vs 2.07±0.09、2.28±0.19 vs 1.33±0.03(P<0.05);M2基因中精氨酸1(Arg1)基因表达水平实验组和对照组分别为0.81±0.21 vs 0.82±0.18、0.66±0.11 vs 0.58±0.09、0.39±0.17 vs 0.37±0.15,甘露糖受体C型2(Mrc2)分别为0.99±0.91 vs 0.97±0.08、0.98±0.12 vs 1.02±0.11、0.59±0.19 vs 0.57±0.08,重组蛋白163(CD163)分别为1.75±0.20 vs 1.69±0.18、0.22±0.02 vs 0.21±0.01、0.04±0.01 vs 0.03±0.01(P>0.05)。结论实验小鼠输注贮存红细胞明显促进其肝脏组织巨噬细胞朝向M1表型的极化。
基金supported by the National Natural Science Foundation of China,No.31372473,30871886the Funding Project for Academic Human Resources Development in Institutions of Higher Learning under the Jurisdiction of Beijing Municipality of China,No.PHR201107134the 2012 Scientific Research Quality Raising Funds of Beijing University of Agriculture of China,No.PXM2012_014207_000010
文摘Most studies on spinal cord neuronal injury have focused on spinal cord tissue histology and the expression of nerve cell damage and repair-related genes. The importance of the microcirculation is often ignored in spinal cord injury and repair research. Therefore, in this study, we established a rat model of intervertebral disc extrusion by inserting a silica gel pad into the left ventral sur-face of T13. Electroacupuncture was used to stimulate the bilateralZusanlipoint （ST36） and Neiting point （ST44） for 14 days. Compared with control animals, blood lfow in the ifrst lumbar vertebra （L1） was noticeably increased in rats given electroacupuncture. Microvessel density in the T13 segment of the spinal cord was increased significantly as well. The number of normal neurons was higher in the ventral horn of the spinal cord. In addition, vacuolation in the white matter was lessened. No obvious glial cell proliferation was visible. Furthermore, hindlimb motor function was improved signiifcantly. Collectively, our results suggest that electroacupuncture can improve neuronal morphology and microcirculation, and promote the recovery of neurological functions in a rat model of intervertebral disc extrusion.
基金Supported by Crohn’s and Colitis Foundation of Canada,No.11883 1486 RR 0001Natural Science and Engineering Re-search Council and the Intestinal Diseases Education Awareness Society,No.86435 5557 RR0001
文摘Intestinal alkaline phosphatase(IAP) plays an essential role in intestinal homeostasis and health through interactions with the resident microbiota, diet and the gut. IAP's role in the intestine is to dephosphorylate toxic microbial ligands such as lipopolysaccharides, unmethylated cytosine-guanosine dinucleotides and flagellin as well as extracellular nucleotides such as uridine diphosphate. IAP's ability to detoxify these ligands is essential in protecting the host from sepsis during acute inflammation and chronic inflammatory conditions such as inflammatory bowel disease. Also important in these complications is IAP's ability to regulate the microbial ecosystem by forming a complex relationship between microbiota, diet and the intestinal mucosal surface. Evidence reveals that diet alters IAP expression and activity and this in turn can influence the gut microbiota and homeostasis. IAP's ability to maintain a healthygastrointestinal tract has accelerated research on its potential use as a therapeutic agent against a multitude of diseases.Exogenous IAP has been shown to have beneficial effects when administered during ulcerative colitis,coronary bypass surgery and sepsis.There are currently a handful of human clinical trials underway investigating the effects of exogenous IAP during sepsis,rheumatoid arthritis and heart surgery.In light of these findings IAP has been marked as a novel agent to help treat a variety of other inflammatory and infectious diseases.The purpose of this review is to highlight the essential characteristics of IAP in protection and maintenance of intestinal homeostasis while addressing the intricate interplay between IAP,diet,microbiota and the intestinal epithelium.
文摘Aim DL0805-2 is a novel Rho-kinases inhibitor which has been found to have potent cardiovascular effects. In the present research, we aimed to study the potential of DL0805-2 in the treatment of pulmonary arterial hypertension （PAH） and discuss the underlying mechanisms preliminarily. Methods A classical PAH animal model was used, which was established by single injection of 50 mg · kg^-1 monocrotaline （MCT）. One week later, the rats were administrated with 1, 3, 10 mg · kg^-1 DL0805-2 via intraperitoneal injection for 18 days. At the end of the experiment, the body weight and survival rate were recorded. Meanwhile, the respiration function, heart function, blood pressure and pulmonary artery pressure were detected. Serum was collected for biochemical index analysis. The weight of vital organs was used to calculate the organ index. Histopathology examination was em-ployed to observe the subtle changes in hearts, vessels and lungs. Furthermore, the mechanisms were studied main- ly by the method of western blotting. Results DL0805-2 did not show significant influence on body weight of PAH rats. But the survival rate of PAH rats treated with 3 and 10 mg · kg^-1 DL0805-2 was increased up to 90. 9% com- pared with the model group （68.2%）. DL0805-2 improved the pulmonary artery blood flow especially the maximal -1 -1 velocity （PV max） from 397.2 cm · s^-1 to 506.5, 540. 1 and 574.0 cm · s^-1 respectively. The results of echocar- diography and electrocardiogram show that DL0805-2 had little effect on left ventricle and systemic circulation but attenuated right ventricle injury and decreased the right ventricle pressure from 73.73 mmHg to 47.80, 42.64 and 46.45 mmHg respectively after DL0805-2 intervention. Disease markers of PAH including NT-proBNP in serum and ET-1 in lung tissue homogenate and serum biochemical indicators, ALT, AST and LDH, were reduced by DL0805-2. DL0805-2 also relieved edema of lungs and decreased inflammatory cytokines production. Through the examination on histopathologic slide of pulmonary main artery, right ventricle and lung, DL0805 derivatives were found to have significant protection effect on structural changes of organs induced by pulmonary hypertension. Ac- cording to the preliminary study on the mechanisms of DL0805-2 in PAH, Rho/ROCK pathway was significantly in- hibited by DL0805 derivatives. In addition, DL0805 derivatives showed effect on BMPRII/p-Smad pathway and ap- optosis related pathway. Conclusion DL0805-2 has showed potent treatment effect on the PAH rats. And the un- derlying mechanisms studies also indicated that RhoA/ROCK and BMPRII pathways were involved. This work will provide basis experimental data for the further research and development of DL0805-2.
