目的:分析CT血流灌注结合血脑屏障标志蛋白对中毒性休克患者神经元损伤的评价价值。方法:选取院内妇产科门诊与住院中毒性休克患者60例及30例健康人员作为观察对象,中毒性休克患者分为轻度与重度两组,观察三组患者相关临床指标。结果:...目的:分析CT血流灌注结合血脑屏障标志蛋白对中毒性休克患者神经元损伤的评价价值。方法:选取院内妇产科门诊与住院中毒性休克患者60例及30例健康人员作为观察对象,中毒性休克患者分为轻度与重度两组,观察三组患者相关临床指标。结果:重度组CT灌注相关指标明显高于其他两组,轻度组明显高于对照组。重度组紧密连接蛋白相关指标表达水平明显除神经元特异性烯醇化酶(Neuron Specific Enolase,NSE)指标外均明显低于其他两组,轻度组除NSE指标外明显低于对照组。三组调查对象CT灌注相关指标及紧密连接蛋白表达均存在显著差异(P<0.05)。结论:中毒性休克患者多伴随神经损伤,而明确此病症临床指标变化规律对于诊治具有重要意义,本次调查证实,CT血流灌注结合血脑屏障标志蛋白能够为中毒性休克患者神经元损伤的发生及发展评估提供可靠的早期预测指标,同时为诊治提供新靶点。展开更多
AIM： To investigate the effect of Lianshu preparation on lipopolysaccharide （LPS）-induced diarrhea in rats. METHODS： A diarrhea model was established in Sprague Dawley rats via injection of 1 mL of 30 mg/kg LPS. A...AIM： To investigate the effect of Lianshu preparation on lipopolysaccharide （LPS）-induced diarrhea in rats. METHODS： A diarrhea model was established in Sprague Dawley rats via injection of 1 mL of 30 mg/kg LPS. A total of 40 rats were randomly divided into normal group, LPS group, LPS ＋ Lianshu group, LPS ＋ berberine group （n = 10 in each group）. Their intestinal mucosal barrier and frequency of diarrhea were observed. Levels of glucose, serum Na^＋, K^＋, Cl and hematocrit, plasma nitrogen monoxide （NO）, diamine oxidase （DAO）, and D （-）-lactate were measured. The number of IgA＋ plasma cells in small intestine was detected and SIgA levels in the intestinal fluid were measured. The antipyretic activity of Lianshu preparation in rats was evaluated using Brewer＇s yeast-induced pyrexia （10 mL/kg of 20% aqueous suspension）. Acetaminophen （250 mg/kg, intragastric administration, bid） was comparison. Temperature used as a standard drug for was recorded 1 h before and 6 h after Brewer＇s yeast injection. Finally, small intestina transmission in mice treated with Lianshu was detected after intraperitoneal injection of methyl prostigmin （2 mg/kg）. Atropine （10 g/kg） was used as a control. The ink content in intestine was determined and the total length of intestine was measured. RESULTS： The frequency of diarrhea was higher in LPS group than in LPS ＋ Lianshu group and LPS ＋ berberine group （36.70± 5.23 vs 28.50 ±4.06 and 32.70±9.30 respectively, P 〈 0.01）, and lower in LP5 ＋ Lianshu group than in LPS ＋ berberine group （P = 0.03）. The levels of Na＋, glucose, Cl, K^＋ were significantly lower in LPS ＋ Lianshu group than in LPS ＋ berberine group （140.35±3.19 mmol/L vs 131.99±4.86 mmol/L, 8.49 ±1.84 mmol/L vs 6.54±2.30 mmol/L, 106.29± 4.41 mmol/L vs 102.5±1.39 mmol/L, 5.08±0.66 mmol/L vs 4.32 ± 0.62 mmol/L respectively, P 〈 0.05）. The level of hematocrit was lower in LPS ＋ Lianshu group than in LPS ＋ berberine group （0.50% ±0.07% vs 0.59%± 0.10% respectively, P 〈 0.05）. The plasma levels of NO, DAO and D （-）-lactate were higher in LPS group than in normal group （79.74 ± 7.39μmol/L vs 24.94 ± 3.38μmol/L, 2.48 ±0.42μ/mL vs 0.82 ±0.33 p/mL, 5.63± 0.85μg/mL vs 2.01 ±0.32 μg/mL respectively, P 〈 0.01）, and lower in LPS ＋ Lianshu group than in LP5 ＋ berberine group （48.59±4.70μmol/L vs 51.56 ±8.38 μmol/L, 1.43± 0.53μmol/mL vs 1.81 ±0.42 μmol/mL, 4.00± 0.54 μg/mL vs 4.88 ± 0.77 pg/mL respectively, P 〈 0.05）. The morphology of the intestinal mucosa showed destroyed villi in LPS group and atrophied intestinal mucosa in other groups. The pathological intestinal mucosal changes were less in LPS ＋ Lianshu group than in LPS group. The number of IgA＋ plasma cells and amount of SIgA were higher in LPS ＋ Lianshu group than in LPS group （1.16±0.19/μm^2 vs 1.09±0.28/μm^2, P = 0.026; 0.59 ±0.12 mg/L vs 0.15± 0.19 mg/L respectively, P = 0.000）. Lianshu had counteractive effects on yeast-induced pyrexia and enterokinesia in rats. CONCLUSION： Lianshu preparation has therapeutic effects on LPS-induced diarrhea and enterokinesia in rats.展开更多
目的:探究水蛭素对急性脑出血患者血脑屏障紧密连接蛋白表达和患者颅内压的影响。方法:选择120例自发性脑出血患者随机分为治疗组(n=60)和对照组(n=60),其中对照组患者实施常规治疗,观察组患者则在对照组的基础上加用水蛭素治疗。对比...目的:探究水蛭素对急性脑出血患者血脑屏障紧密连接蛋白表达和患者颅内压的影响。方法:选择120例自发性脑出血患者随机分为治疗组(n=60)和对照组(n=60),其中对照组患者实施常规治疗,观察组患者则在对照组的基础上加用水蛭素治疗。对比分析两组患者血脑屏障紧密连接蛋白claudin-5、蛋白酪氨酸激酶2/信号转导(janus kinase 2/signal transducer,JAK2)、转录激活因子3(activator of transcription 3,STAT3)和细胞间黏附分子-1(Intercellular cell adhesion molecule-1,ICAM-1)mRNA的表达水平,同时分析颅内压、临床治疗效果、出血量、血肿周围低密度,以及神经功能缺损(European stroke scale,ESS)和生活质量(The MOS item short from health survey-36,SF36)评分。结果:治疗4d、10d和21d,两组患者claudin-5水平、ESS和SF36评分均较治疗前升高,且治疗组水平显著高于对照组,差异均有统计学意义(P<0.05);JAK2、STAT3、ICAM-1 mRNA水平、颅内压、出血量和血肿周围低密度均较治疗前降低,且治疗组水平显著低于对照组,差异均有统计学意义(P<0.05)。另外,观察组患者治疗总有效率为96.67%,显著高于对照组的88.33%,差异有统计学意义(P<0.05)。结论:水蛭素可减轻急性脑出血患者JAK2、STAT3和ICAM-1 mRNA的高表达,提高血脑屏障紧密连接蛋白claudin-5的表达水平,降低颅内压,促进脑出血水肿的吸收,缩小血肿周围低密度区,从而促进患者神经功能恢复,提高生活质量。展开更多
Brain metastases are common intracranial tumors, and their occurrence not only represents a high degree of malignancy, but also often is the major factor in treatment failure and poor prognosis. Primary site of brain ...Brain metastases are common intracranial tumors, and their occurrence not only represents a high degree of malignancy, but also often is the major factor in treatment failure and poor prognosis. Primary site of brain metastases often occur in lung. P-glycoprotein is a member of the （ATP binding cassette） transporter superfamily,which is closely related to the development of lung metastases. It is the main reason for influencing the drug through the blood_brain barrier into the brain tissue, and it also is an important factor affecting the treatment of brain metastases. According to the theory of traditional chinese mddicine, the pathogenesis of brain metastases is due to phlegm, poison, stasis, virtual and so on. The principle of treatment is to promote blood circulation, remove phlegm turbidity. In recent years, the impact of Chinese herbal medicine on P-glycoprotein is increasing. This paper analyzes the mechanism and components of the relevant Chinese medicine on P-glycoprotein. It provides a reference for clinical rational drug use.展开更多
Cromakalim,an adenosine triphosphate-sensitive potassium channel opener,exhibits protective effects on cerebral ischemia/reperfusion injury.However,there is controversy as to whether this effect is associated with aqu...Cromakalim,an adenosine triphosphate-sensitive potassium channel opener,exhibits protective effects on cerebral ischemia/reperfusion injury.However,there is controversy as to whether this effect is associated with aquaporin-4 and blood-brain barrier permeability.Immunohistochemistry results show that preventive administration of cromakalim decreased aquaporin-4 and IgG protein expression in rats with ischemia/reperfusion injury;it also reduced blood-brain barrier permeability,and alleviated brain edema,ultimately providing neuroprotection.展开更多
We investigated the effects of glucosamine(GS) on blood-brain barrier(BBB) function and matrix metalloproteinase-9 (MMP-9) expression in rats with experimental autoimmune encephalomyelitis(EAE).Animals were randomly d...We investigated the effects of glucosamine(GS) on blood-brain barrier(BBB) function and matrix metalloproteinase-9 (MMP-9) expression in rats with experimental autoimmune encephalomyelitis(EAE).Animals were randomly divided into three groups,among which the EAE and GS groups were immunized with complete antigen and pertussis toxin,and the adjuvant group was immunized with complete Freund's adjuvant and pertussis toxin.Rats were treated by peritoneal injection of GS 180 mg/(kg·d) in the GS group and peritoneal injection of phosphate-buffered saline 4.5 mL/(kg·d) in the EAE and adjuvant groups.We proposed to assess the integrity of BBB by calculating cerebrospinal fluid to serum albumin quotient(QA) on days 6,8,10,12,14,16 and 18 post-immunization.At the same time,the brains and spinal cords were removed for MMP-9 immunohistochemical staining. Experiments demonstrated that in the EAE group,QA value and MMP-9 expression were highly elevated and up-regulated and correlated to disease severity.Moreover,there was statistically significantly positive correlation between QA value and MMP-9 expression.In the GS group,we observed that the mean disease onset date was delayed,the incidence and mean score of symptom were suppressed at the peak phase of disease(P<0.05).Furthermore,QA value and MMP-9 expression in the GS group showed stronger inhibition when compared with those of the EAE group(P<0.05).Our study showed that GS would reduce the BBB breakdown and leukocyte trafficking by inhibiting the production of MMP-9 and mitigate EAE.展开更多
Ischemic stroke seriously threatens human health and quality of life.Xiao-Xu-Ming(XXM)decoction has been a classical prescription for stroke therapy.In our previous studies,we have found that XXM exerts neuroprotectiv...Ischemic stroke seriously threatens human health and quality of life.Xiao-Xu-Ming(XXM)decoction has been a classical prescription for stroke therapy.In our previous studies,we have found that XXM exerts neuroprotective effects,improves brain injury,and attenuates neuroinflammation in cerebral ischemia rats.In this study,we investigated the effects and possible mechanism of XXM on thrombotic focal cerebral ischemia.After treatment with XXM,the neurological function and motor abilities were improved,and cerebral infarction volume was significantly decreased compared with rats of thrombotic focal cerebral ischemia.Besides,the results of BBB integrity detected by EB leakage and tight junction(TJ)protein expression showed that XXM could maintain BBB integrity and improve the expressions of TJ proteins,including claudin-1,occluding,and ZO-1,in the ischemic ipsilateral cortex disrupted by thrombotic cerebral ischemia.Furthermore,proteomic techniques were used to identify the differentially expressed proteins(DEPs)in the ischemic cerebral cortex,and the results showed that 132 DEPs regulated by XXM were detected in the ischemic cerebral cortex.Bioinformatic analysis showed that these regulated proteins by XXM were mainly involved in complement and coagulation cascade,and lysosome,etc.Furthermore,there was an interaction among DEPs,including Lgals3,Ctsz,Capg,C1qa,S100a4,Grn,Hspb1,Aif1,and Anxa1,etc.In conclusion,XXM ameliorated brain injury of thrombotic focal ischemic stroke,and Lgals3,Ctsz,Capg,C1qa,S100a4,Grn,Hspb1,Aif1,and Anxa1 could help provide possible therapeutic targets of XXM for ischemic stroke and offer research direction for further research.展开更多
文摘目的:分析CT血流灌注结合血脑屏障标志蛋白对中毒性休克患者神经元损伤的评价价值。方法:选取院内妇产科门诊与住院中毒性休克患者60例及30例健康人员作为观察对象,中毒性休克患者分为轻度与重度两组,观察三组患者相关临床指标。结果:重度组CT灌注相关指标明显高于其他两组,轻度组明显高于对照组。重度组紧密连接蛋白相关指标表达水平明显除神经元特异性烯醇化酶(Neuron Specific Enolase,NSE)指标外均明显低于其他两组,轻度组除NSE指标外明显低于对照组。三组调查对象CT灌注相关指标及紧密连接蛋白表达均存在显著差异(P<0.05)。结论:中毒性休克患者多伴随神经损伤,而明确此病症临床指标变化规律对于诊治具有重要意义,本次调查证实,CT血流灌注结合血脑屏障标志蛋白能够为中毒性休克患者神经元损伤的发生及发展评估提供可靠的早期预测指标,同时为诊治提供新靶点。
基金Supported by State Administration of Chinese Medicine,No.04-06LP24Health Bureau of Shanghai,No.06ER14090the Major State Basic Research Development Program of China "973 Program",No.2006CB504810
文摘AIM： To investigate the effect of Lianshu preparation on lipopolysaccharide （LPS）-induced diarrhea in rats. METHODS： A diarrhea model was established in Sprague Dawley rats via injection of 1 mL of 30 mg/kg LPS. A total of 40 rats were randomly divided into normal group, LPS group, LPS ＋ Lianshu group, LPS ＋ berberine group （n = 10 in each group）. Their intestinal mucosal barrier and frequency of diarrhea were observed. Levels of glucose, serum Na^＋, K^＋, Cl and hematocrit, plasma nitrogen monoxide （NO）, diamine oxidase （DAO）, and D （-）-lactate were measured. The number of IgA＋ plasma cells in small intestine was detected and SIgA levels in the intestinal fluid were measured. The antipyretic activity of Lianshu preparation in rats was evaluated using Brewer＇s yeast-induced pyrexia （10 mL/kg of 20% aqueous suspension）. Acetaminophen （250 mg/kg, intragastric administration, bid） was comparison. Temperature used as a standard drug for was recorded 1 h before and 6 h after Brewer＇s yeast injection. Finally, small intestina transmission in mice treated with Lianshu was detected after intraperitoneal injection of methyl prostigmin （2 mg/kg）. Atropine （10 g/kg） was used as a control. The ink content in intestine was determined and the total length of intestine was measured. RESULTS： The frequency of diarrhea was higher in LPS group than in LPS ＋ Lianshu group and LPS ＋ berberine group （36.70± 5.23 vs 28.50 ±4.06 and 32.70±9.30 respectively, P 〈 0.01）, and lower in LP5 ＋ Lianshu group than in LPS ＋ berberine group （P = 0.03）. The levels of Na＋, glucose, Cl, K^＋ were significantly lower in LPS ＋ Lianshu group than in LPS ＋ berberine group （140.35±3.19 mmol/L vs 131.99±4.86 mmol/L, 8.49 ±1.84 mmol/L vs 6.54±2.30 mmol/L, 106.29± 4.41 mmol/L vs 102.5±1.39 mmol/L, 5.08±0.66 mmol/L vs 4.32 ± 0.62 mmol/L respectively, P 〈 0.05）. The level of hematocrit was lower in LPS ＋ Lianshu group than in LPS ＋ berberine group （0.50% ±0.07% vs 0.59%± 0.10% respectively, P 〈 0.05）. The plasma levels of NO, DAO and D （-）-lactate were higher in LPS group than in normal group （79.74 ± 7.39μmol/L vs 24.94 ± 3.38μmol/L, 2.48 ±0.42μ/mL vs 0.82 ±0.33 p/mL, 5.63± 0.85μg/mL vs 2.01 ±0.32 μg/mL respectively, P 〈 0.01）, and lower in LPS ＋ Lianshu group than in LP5 ＋ berberine group （48.59±4.70μmol/L vs 51.56 ±8.38 μmol/L, 1.43± 0.53μmol/mL vs 1.81 ±0.42 μmol/mL, 4.00± 0.54 μg/mL vs 4.88 ± 0.77 pg/mL respectively, P 〈 0.05）. The morphology of the intestinal mucosa showed destroyed villi in LPS group and atrophied intestinal mucosa in other groups. The pathological intestinal mucosal changes were less in LPS ＋ Lianshu group than in LPS group. The number of IgA＋ plasma cells and amount of SIgA were higher in LPS ＋ Lianshu group than in LPS group （1.16±0.19/μm^2 vs 1.09±0.28/μm^2, P = 0.026; 0.59 ±0.12 mg/L vs 0.15± 0.19 mg/L respectively, P = 0.000）. Lianshu had counteractive effects on yeast-induced pyrexia and enterokinesia in rats. CONCLUSION： Lianshu preparation has therapeutic effects on LPS-induced diarrhea and enterokinesia in rats.
文摘目的:探究水蛭素对急性脑出血患者血脑屏障紧密连接蛋白表达和患者颅内压的影响。方法:选择120例自发性脑出血患者随机分为治疗组(n=60)和对照组(n=60),其中对照组患者实施常规治疗,观察组患者则在对照组的基础上加用水蛭素治疗。对比分析两组患者血脑屏障紧密连接蛋白claudin-5、蛋白酪氨酸激酶2/信号转导(janus kinase 2/signal transducer,JAK2)、转录激活因子3(activator of transcription 3,STAT3)和细胞间黏附分子-1(Intercellular cell adhesion molecule-1,ICAM-1)mRNA的表达水平,同时分析颅内压、临床治疗效果、出血量、血肿周围低密度,以及神经功能缺损(European stroke scale,ESS)和生活质量(The MOS item short from health survey-36,SF36)评分。结果:治疗4d、10d和21d,两组患者claudin-5水平、ESS和SF36评分均较治疗前升高,且治疗组水平显著高于对照组,差异均有统计学意义(P<0.05);JAK2、STAT3、ICAM-1 mRNA水平、颅内压、出血量和血肿周围低密度均较治疗前降低,且治疗组水平显著低于对照组,差异均有统计学意义(P<0.05)。另外,观察组患者治疗总有效率为96.67%,显著高于对照组的88.33%,差异有统计学意义(P<0.05)。结论:水蛭素可减轻急性脑出血患者JAK2、STAT3和ICAM-1 mRNA的高表达,提高血脑屏障紧密连接蛋白claudin-5的表达水平,降低颅内压,促进脑出血水肿的吸收,缩小血肿周围低密度区,从而促进患者神经功能恢复,提高生活质量。
文摘Brain metastases are common intracranial tumors, and their occurrence not only represents a high degree of malignancy, but also often is the major factor in treatment failure and poor prognosis. Primary site of brain metastases often occur in lung. P-glycoprotein is a member of the （ATP binding cassette） transporter superfamily,which is closely related to the development of lung metastases. It is the main reason for influencing the drug through the blood_brain barrier into the brain tissue, and it also is an important factor affecting the treatment of brain metastases. According to the theory of traditional chinese mddicine, the pathogenesis of brain metastases is due to phlegm, poison, stasis, virtual and so on. The principle of treatment is to promote blood circulation, remove phlegm turbidity. In recent years, the impact of Chinese herbal medicine on P-glycoprotein is increasing. This paper analyzes the mechanism and components of the relevant Chinese medicine on P-glycoprotein. It provides a reference for clinical rational drug use.
基金the Shandong Provincial Science and Technology Program,No. 2006GG202004
文摘Cromakalim,an adenosine triphosphate-sensitive potassium channel opener,exhibits protective effects on cerebral ischemia/reperfusion injury.However,there is controversy as to whether this effect is associated with aquaporin-4 and blood-brain barrier permeability.Immunohistochemistry results show that preventive administration of cromakalim decreased aquaporin-4 and IgG protein expression in rats with ischemia/reperfusion injury;it also reduced blood-brain barrier permeability,and alleviated brain edema,ultimately providing neuroprotection.
基金Natural Science Foundation of Shanxi,China (Grant No.2008011082-1)Shanxi Scholarship Council of China (Grant No.2008-86)Natural Science Foundation of Shanxi Datong University(Grant No.2009Q6).
文摘We investigated the effects of glucosamine(GS) on blood-brain barrier(BBB) function and matrix metalloproteinase-9 (MMP-9) expression in rats with experimental autoimmune encephalomyelitis(EAE).Animals were randomly divided into three groups,among which the EAE and GS groups were immunized with complete antigen and pertussis toxin,and the adjuvant group was immunized with complete Freund's adjuvant and pertussis toxin.Rats were treated by peritoneal injection of GS 180 mg/(kg·d) in the GS group and peritoneal injection of phosphate-buffered saline 4.5 mL/(kg·d) in the EAE and adjuvant groups.We proposed to assess the integrity of BBB by calculating cerebrospinal fluid to serum albumin quotient(QA) on days 6,8,10,12,14,16 and 18 post-immunization.At the same time,the brains and spinal cords were removed for MMP-9 immunohistochemical staining. Experiments demonstrated that in the EAE group,QA value and MMP-9 expression were highly elevated and up-regulated and correlated to disease severity.Moreover,there was statistically significantly positive correlation between QA value and MMP-9 expression.In the GS group,we observed that the mean disease onset date was delayed,the incidence and mean score of symptom were suppressed at the peak phase of disease(P<0.05).Furthermore,QA value and MMP-9 expression in the GS group showed stronger inhibition when compared with those of the EAE group(P<0.05).Our study showed that GS would reduce the BBB breakdown and leukocyte trafficking by inhibiting the production of MMP-9 and mitigate EAE.
基金The National Natural Science Foundation of China (Grant No. 81473383)the Significant New-Drugs Creation of Science and Technology Major Projects (Grant No. 2018ZX09711001-003-019)+1 种基金the Medical and Health Innovation Project of Chinese Academy of Medical Sciences (Grant No. 2016-I2M-3-007)Innovation Fund for Graduate of Beijing Union Medical College (Grant No. 2018-1007-04)。
文摘Ischemic stroke seriously threatens human health and quality of life.Xiao-Xu-Ming(XXM)decoction has been a classical prescription for stroke therapy.In our previous studies,we have found that XXM exerts neuroprotective effects,improves brain injury,and attenuates neuroinflammation in cerebral ischemia rats.In this study,we investigated the effects and possible mechanism of XXM on thrombotic focal cerebral ischemia.After treatment with XXM,the neurological function and motor abilities were improved,and cerebral infarction volume was significantly decreased compared with rats of thrombotic focal cerebral ischemia.Besides,the results of BBB integrity detected by EB leakage and tight junction(TJ)protein expression showed that XXM could maintain BBB integrity and improve the expressions of TJ proteins,including claudin-1,occluding,and ZO-1,in the ischemic ipsilateral cortex disrupted by thrombotic cerebral ischemia.Furthermore,proteomic techniques were used to identify the differentially expressed proteins(DEPs)in the ischemic cerebral cortex,and the results showed that 132 DEPs regulated by XXM were detected in the ischemic cerebral cortex.Bioinformatic analysis showed that these regulated proteins by XXM were mainly involved in complement and coagulation cascade,and lysosome,etc.Furthermore,there was an interaction among DEPs,including Lgals3,Ctsz,Capg,C1qa,S100a4,Grn,Hspb1,Aif1,and Anxa1,etc.In conclusion,XXM ameliorated brain injury of thrombotic focal ischemic stroke,and Lgals3,Ctsz,Capg,C1qa,S100a4,Grn,Hspb1,Aif1,and Anxa1 could help provide possible therapeutic targets of XXM for ischemic stroke and offer research direction for further research.
