AIM To explore the kinetic changes in plasma D(-)- lactate and lipopolyssccharide(LPS)levels,and investigate whether D(-)-lactate could be used as a marker of intestinal injury in rats following gut ischemia/ reperfus...AIM To explore the kinetic changes in plasma D(-)- lactate and lipopolyssccharide(LPS)levels,and investigate whether D(-)-lactate could be used as a marker of intestinal injury in rats following gut ischemia/ reperfusion,burn,and acute necrotizing pancreatitis (ANP). METHODS Three models were developed in rats:① gut ischemia/ reperfusion obtained by one hour of superior mesenteric artery occlusion followed by reperfusion;② severe burn injury created by 30% of total body surface area(TBSA)full-thickness scald burn;and ③ ANP induced by continuous inverse infusion of sodium taurocholate and trypsin into main pancreatic duct. Plasma levels of D(-)-lactate in systemic circulation and LPS in portal circulation were measured by enzymatic- spectrophotometric method and limulus amebocyte lysate (LAL)test kit,respectively.Tissue samples of intestine were taken for histological analysis. RESULTS One hour gut ischemia followed by reperfusion injuries resulted in a significant elevation in plasma D(-)- lactate and LPS levels,and there was a significant correlation between the plasma D(-)-lactate and LPS(r =0.719,P<0.05).The plasma concentrations of D(-)- lactate and LPS increased significantly at 6h postburn, and there was also a remarkable correlation between them (r = 0.877,P < 0.01).D(-)-lactate and LPS levels elevated significantly at 2h after ANP,with a similar significant correlation between the two levels(r = 0.798, P < 0.01 ).The desquamation of intestine villi and infiltration of inflammatory cells in the lamina propria were observed in all groups. CONCLUSION The changes of plasma D(-)-lactate levels in systemic blood paralleled with LPS levels in the portal vein blood.The measurement of plasma D(-)-lactate level may be a useful marker to assess the intestinal injury and to monitor an increase of intestinal permeability and endotoxemia following severe injuries in early stage.展开更多
BACKGROUND: Plasma D(-)-lactate and diamine oxidase (DAO) can reflect patients' intestinal mucosal condition. We evaluated the changes of plasma D (-)-lactate, DAO and endotoxin activities and their significance i...BACKGROUND: Plasma D(-)-lactate and diamine oxidase (DAO) can reflect patients' intestinal mucosal condition. We evaluated the changes of plasma D (-)-lactate, DAO and endotoxin activities and their significance in patients with liver cirrhosis. METHODS: Fifty liver cirrhosis patients were enrolled into experimental group and 30 healthy people into control group. The plasma levels of D(-)-lactate, DAO and endo- toxin were detected spectrophotographically. RESULTS: The level of D(-)-lactate was significantly high- er in the experimental group than that in the control group (P<0.01). Significant differences of D (-)-lactate levels were observed in Child-Pugh subgroups of the experimen- tal group (P <0. 01). The level of DAO was significantly higher in the experimental group than that in the control group (P <0.01), but the level of DAO in Child-Pugh sub- group C was significantly lower than that in Child-Pugh subgroup B (P<0.01). The level of endotoxin was signifi- cantly increased in the experimental group except Child Pugh subgroup A (P<0.01). The plasma levels of D(-) lactate, DAO and endotoxin were positively correlated with each other (P<0.01). CONCLUSIONS: The data suggest that both plasma D(-) lactate and DAO activity are sensitive markers for early diagnosis of gut failure and endotoxemia in patients with liver cirrhosis. The impairment of intestinal barrier func- tion may be one of the critical reasons for deterioration of liver cirrhosis.展开更多
Objective To study the potential role of tumor necrosis factor-α (TNF-α) induction in the development of mucosal barrier dysfunction in rats caused by acute intestinal ischemia-reperfusion injury, and to examine whe...Objective To study the potential role of tumor necrosis factor-α (TNF-α) induction in the development of mucosal barrier dysfunction in rats caused by acute intestinal ischemia-reperfusion injury, and to examine whether pretreatment with monoclonal antibody against TNF-α (TNF-α MoAb) would affect the release of D(-)-lactate after local gut ischemia followed by reperfusion. Methods Anesthetized Sprague-Dawley rats underwent superior mesenteric artery occlusion for 75 min followed by reperfusion for 6 hr. The rats were treated intravenously with either TNF-α MoAb (20 mg/kg) or albumin (20 mg/kg) 30 min prior to the onset of ischemia. Plasma D(-)-lactate levels were measured in both the portal and systemic blood by an enzymatic spectrophotometric assay. Intestinal TNF-αmRNA expression as well as protein levels were also measured at various intervals. In addition, a postmortem examination was performed together with a macropathological evaluation based on a four-grade scoring system.Results Intestinal ischemia resulted in a significant elevation in D(-)-lactate levels in the portal vein blood in both the control and treatment groups ( P ＜0.05). However, animals pretreated with TNF-α MoAb at 6 hr after reperfusion showed significant attenuation of an increase in both portal and systemic D(-)-lactate levels when compared with those only receiving albumin (P ＜ 0.05). In the control animals, a remarkable rise in intestinal TNF-α level was measured at 0.5 hr after clamp release ( P ＜ 0.01); however, prophylactic treatment with TNF-α MoAb completely annulled the increase of local TNF-α levels seen in the control animals. Similarly, after anti-TNF-α MoAb administration, intestinal TNF-α mRNA expression was markedly inhibited, which showed significant differences when compared with the control group at 0.5 hr, 2 hr and 6 hr after the release of occlusion ( P ＜ 0.05-0.01 ). In addition, the pathological examination showed marked intestinal lesions that formed during ischemia, which were much worse upon reperfusion,particularly at the 6 hr time point. These acute injuries were obviously attenuated in animals receiving TNF-α MoAb.Conclusions It appeared that acute intestinal ischemia was associated with failure of the mucosal barrier, resulting in increased plasma D(-)-lactate levels in both portal and systemic blood. These results suggest that TNF-α appears to be involved in the development of local damage associated with intestinal ischemic injury. Moreover, prophylactic treatment with TNF-α MoAb exerts preventive effects on ischemia/ reperfusion-induced circulating D (-)-lactate elevation and gut injury. ( J Geriatr Cardiol 2004;1(2):119-124. )展开更多
目的分析2型糖尿病患者25-羟维生素D[25(OH)D]水平,初步了解血清25(OH)D水平与2型糖尿病患者糖化血红蛋白(HbA1c)、胰岛功能等代谢指标的相关性。方法选择新乡市第一人民医院内分泌科2020年1月至2020年12月收治的459例2型糖尿病患者为...目的分析2型糖尿病患者25-羟维生素D[25(OH)D]水平,初步了解血清25(OH)D水平与2型糖尿病患者糖化血红蛋白(HbA1c)、胰岛功能等代谢指标的相关性。方法选择新乡市第一人民医院内分泌科2020年1月至2020年12月收治的459例2型糖尿病患者为研究对象。收集患者的临床资料,包括性别、年龄、血清25(OH)D、空腹胰岛素、C肽、HbA1c、空腹血糖、餐后血糖、尿微量白蛋白、尿白蛋白肌酐比值、血钙、血尿酸(UA)、三酰甘油(TG)、总胆固醇(TCH)、低密度脂蛋白(LDL)、高密度脂蛋白(HDL)等。根据血清25(OH)D水平将患者分为充足组[n=20,25(OH)D≥30μg·L^(-1)]、不足组[n=95,20μg·L^(-1)≤25(OH)D<30μg·L^(-1)]、缺乏组[n=231,10μg·L^(-1)≤25(OH)D<20μg·L^(-1)]、严重缺乏组[n=113,25(OH)D<10μg·L^(-1)]。比较4组患者各代谢指标的差异,采用Pearson相关分析25(OH)D与各代谢指标的相关性。结果2型糖尿病患者血清25(OH)D水平为3.00~46.59(15.75±0.35)μg·L^(-1),男性患者的血清25(OH)D水平显著高于女性患者(P<0.05)。2型糖尿病患者25(OH)D缺乏的患病率为74.9%(344/459),25(OH)D缺乏主要发生在1、2、3、4、11、12月份。不足组、缺乏组和严重缺乏组患者HbA1c显著高于充足组(P<0.05),缺乏组和严重缺乏组患者HbA1c显著高于不足组(P<0.05);缺乏组和严重缺乏组患者HbA1c比较差异无统计学意义(P>0.05)。充足组与不足组、缺乏组与严重缺乏组患者空腹血糖比较差异无统计学意义(P>0.05);缺乏组和严重缺乏组患者空腹血糖显著高于充足组、不足组(P<0.05)。充足组、不足组、缺乏组患者空腹胰岛素、尿微量白蛋白、日尿白蛋白总量、尿白蛋白肌酐比值比较差异无统计学意义(P>0.05);严重缺乏组患者空腹胰岛素显著低于充足组、不足组和缺乏组,尿微量白蛋白、日尿白蛋白总量、尿白蛋白肌酐比值显著高于充足组、不足组和缺乏组(P<0.05)。4组患者的稳态模型评估的胰岛素抵抗指数(HOMA-IR)、血清白蛋白、血肌酐、餐后1 h血糖、餐后2 h血糖、餐后3 h血糖、空腹C肽、餐后1 h C肽、餐后2 h C肽、餐后3 h C肽、TG、TCH、LDL、HDL、血UA、血钙比较差异均无统计学意义(P>0.05)。Pearson相关性分析结果显示,2型糖尿病患者血清25(OH)D水平与HbA1c、尿微量白蛋白、尿白蛋白肌酐比值呈负相关(r=-0.093、-0.166、-0.157,P<0.05),与空腹胰岛素呈正相关(r=0.089,P<0.05)。2型糖尿病患者血清25(OH)D水平与空腹血糖、HOMA-IR、血清白蛋白、血肌酐、餐后1 h血糖、餐后2 h血糖、餐后3 h血糖、空腹C肽、餐后1 h C肽、餐后2 h C肽、餐后3 h C肽、TG、TCH、LDL、HDL、血UA、血钙等无相关性(P>0.05)。结论2型糖尿病患者25(OH)D缺乏与不足普遍存在,女性患者缺乏更明显。2型糖尿病患者25(OH)D水平与空腹胰岛素呈正相关,与HbA1c、尿微量白蛋白、尿白蛋白肌酐比值呈负相关,25(OH)D缺乏的2型糖尿病患者主要分布在1、2、3、4、11、12月份。展开更多
基金the Fund for National Outstanding Young Researchers of China
文摘AIM To explore the kinetic changes in plasma D(-)- lactate and lipopolyssccharide(LPS)levels,and investigate whether D(-)-lactate could be used as a marker of intestinal injury in rats following gut ischemia/ reperfusion,burn,and acute necrotizing pancreatitis (ANP). METHODS Three models were developed in rats:① gut ischemia/ reperfusion obtained by one hour of superior mesenteric artery occlusion followed by reperfusion;② severe burn injury created by 30% of total body surface area(TBSA)full-thickness scald burn;and ③ ANP induced by continuous inverse infusion of sodium taurocholate and trypsin into main pancreatic duct. Plasma levels of D(-)-lactate in systemic circulation and LPS in portal circulation were measured by enzymatic- spectrophotometric method and limulus amebocyte lysate (LAL)test kit,respectively.Tissue samples of intestine were taken for histological analysis. RESULTS One hour gut ischemia followed by reperfusion injuries resulted in a significant elevation in plasma D(-)- lactate and LPS levels,and there was a significant correlation between the plasma D(-)-lactate and LPS(r =0.719,P<0.05).The plasma concentrations of D(-)- lactate and LPS increased significantly at 6h postburn, and there was also a remarkable correlation between them (r = 0.877,P < 0.01).D(-)-lactate and LPS levels elevated significantly at 2h after ANP,with a similar significant correlation between the two levels(r = 0.798, P < 0.01 ).The desquamation of intestine villi and infiltration of inflammatory cells in the lamina propria were observed in all groups. CONCLUSION The changes of plasma D(-)-lactate levels in systemic blood paralleled with LPS levels in the portal vein blood.The measurement of plasma D(-)-lactate level may be a useful marker to assess the intestinal injury and to monitor an increase of intestinal permeability and endotoxemia following severe injuries in early stage.
文摘BACKGROUND: Plasma D(-)-lactate and diamine oxidase (DAO) can reflect patients' intestinal mucosal condition. We evaluated the changes of plasma D (-)-lactate, DAO and endotoxin activities and their significance in patients with liver cirrhosis. METHODS: Fifty liver cirrhosis patients were enrolled into experimental group and 30 healthy people into control group. The plasma levels of D(-)-lactate, DAO and endo- toxin were detected spectrophotographically. RESULTS: The level of D(-)-lactate was significantly high- er in the experimental group than that in the control group (P<0.01). Significant differences of D (-)-lactate levels were observed in Child-Pugh subgroups of the experimen- tal group (P <0. 01). The level of DAO was significantly higher in the experimental group than that in the control group (P <0.01), but the level of DAO in Child-Pugh sub- group C was significantly lower than that in Child-Pugh subgroup B (P<0.01). The level of endotoxin was signifi- cantly increased in the experimental group except Child Pugh subgroup A (P<0.01). The plasma levels of D(-) lactate, DAO and endotoxin were positively correlated with each other (P<0.01). CONCLUSIONS: The data suggest that both plasma D(-) lactate and DAO activity are sensitive markers for early diagnosis of gut failure and endotoxemia in patients with liver cirrhosis. The impairment of intestinal barrier func- tion may be one of the critical reasons for deterioration of liver cirrhosis.
基金supported in part by grants from the National Key Program for Fundamental Research and Development(973 Project,Grant No.G1999054203)National Natural Science Outstanding Youth Foundation(Grant No.30125020)the National Natural Science Foundation(Grant No.39870286,30200293)of China.
文摘Objective To study the potential role of tumor necrosis factor-α (TNF-α) induction in the development of mucosal barrier dysfunction in rats caused by acute intestinal ischemia-reperfusion injury, and to examine whether pretreatment with monoclonal antibody against TNF-α (TNF-α MoAb) would affect the release of D(-)-lactate after local gut ischemia followed by reperfusion. Methods Anesthetized Sprague-Dawley rats underwent superior mesenteric artery occlusion for 75 min followed by reperfusion for 6 hr. The rats were treated intravenously with either TNF-α MoAb (20 mg/kg) or albumin (20 mg/kg) 30 min prior to the onset of ischemia. Plasma D(-)-lactate levels were measured in both the portal and systemic blood by an enzymatic spectrophotometric assay. Intestinal TNF-αmRNA expression as well as protein levels were also measured at various intervals. In addition, a postmortem examination was performed together with a macropathological evaluation based on a four-grade scoring system.Results Intestinal ischemia resulted in a significant elevation in D(-)-lactate levels in the portal vein blood in both the control and treatment groups ( P ＜0.05). However, animals pretreated with TNF-α MoAb at 6 hr after reperfusion showed significant attenuation of an increase in both portal and systemic D(-)-lactate levels when compared with those only receiving albumin (P ＜ 0.05). In the control animals, a remarkable rise in intestinal TNF-α level was measured at 0.5 hr after clamp release ( P ＜ 0.01); however, prophylactic treatment with TNF-α MoAb completely annulled the increase of local TNF-α levels seen in the control animals. Similarly, after anti-TNF-α MoAb administration, intestinal TNF-α mRNA expression was markedly inhibited, which showed significant differences when compared with the control group at 0.5 hr, 2 hr and 6 hr after the release of occlusion ( P ＜ 0.05-0.01 ). In addition, the pathological examination showed marked intestinal lesions that formed during ischemia, which were much worse upon reperfusion,particularly at the 6 hr time point. These acute injuries were obviously attenuated in animals receiving TNF-α MoAb.Conclusions It appeared that acute intestinal ischemia was associated with failure of the mucosal barrier, resulting in increased plasma D(-)-lactate levels in both portal and systemic blood. These results suggest that TNF-α appears to be involved in the development of local damage associated with intestinal ischemic injury. Moreover, prophylactic treatment with TNF-α MoAb exerts preventive effects on ischemia/ reperfusion-induced circulating D (-)-lactate elevation and gut injury. ( J Geriatr Cardiol 2004;1(2):119-124. )
文摘目的分析2型糖尿病患者25-羟维生素D[25(OH)D]水平,初步了解血清25(OH)D水平与2型糖尿病患者糖化血红蛋白(HbA1c)、胰岛功能等代谢指标的相关性。方法选择新乡市第一人民医院内分泌科2020年1月至2020年12月收治的459例2型糖尿病患者为研究对象。收集患者的临床资料,包括性别、年龄、血清25(OH)D、空腹胰岛素、C肽、HbA1c、空腹血糖、餐后血糖、尿微量白蛋白、尿白蛋白肌酐比值、血钙、血尿酸(UA)、三酰甘油(TG)、总胆固醇(TCH)、低密度脂蛋白(LDL)、高密度脂蛋白(HDL)等。根据血清25(OH)D水平将患者分为充足组[n=20,25(OH)D≥30μg·L^(-1)]、不足组[n=95,20μg·L^(-1)≤25(OH)D<30μg·L^(-1)]、缺乏组[n=231,10μg·L^(-1)≤25(OH)D<20μg·L^(-1)]、严重缺乏组[n=113,25(OH)D<10μg·L^(-1)]。比较4组患者各代谢指标的差异,采用Pearson相关分析25(OH)D与各代谢指标的相关性。结果2型糖尿病患者血清25(OH)D水平为3.00~46.59(15.75±0.35)μg·L^(-1),男性患者的血清25(OH)D水平显著高于女性患者(P<0.05)。2型糖尿病患者25(OH)D缺乏的患病率为74.9%(344/459),25(OH)D缺乏主要发生在1、2、3、4、11、12月份。不足组、缺乏组和严重缺乏组患者HbA1c显著高于充足组(P<0.05),缺乏组和严重缺乏组患者HbA1c显著高于不足组(P<0.05);缺乏组和严重缺乏组患者HbA1c比较差异无统计学意义(P>0.05)。充足组与不足组、缺乏组与严重缺乏组患者空腹血糖比较差异无统计学意义(P>0.05);缺乏组和严重缺乏组患者空腹血糖显著高于充足组、不足组(P<0.05)。充足组、不足组、缺乏组患者空腹胰岛素、尿微量白蛋白、日尿白蛋白总量、尿白蛋白肌酐比值比较差异无统计学意义(P>0.05);严重缺乏组患者空腹胰岛素显著低于充足组、不足组和缺乏组,尿微量白蛋白、日尿白蛋白总量、尿白蛋白肌酐比值显著高于充足组、不足组和缺乏组(P<0.05)。4组患者的稳态模型评估的胰岛素抵抗指数(HOMA-IR)、血清白蛋白、血肌酐、餐后1 h血糖、餐后2 h血糖、餐后3 h血糖、空腹C肽、餐后1 h C肽、餐后2 h C肽、餐后3 h C肽、TG、TCH、LDL、HDL、血UA、血钙比较差异均无统计学意义(P>0.05)。Pearson相关性分析结果显示,2型糖尿病患者血清25(OH)D水平与HbA1c、尿微量白蛋白、尿白蛋白肌酐比值呈负相关(r=-0.093、-0.166、-0.157,P<0.05),与空腹胰岛素呈正相关(r=0.089,P<0.05)。2型糖尿病患者血清25(OH)D水平与空腹血糖、HOMA-IR、血清白蛋白、血肌酐、餐后1 h血糖、餐后2 h血糖、餐后3 h血糖、空腹C肽、餐后1 h C肽、餐后2 h C肽、餐后3 h C肽、TG、TCH、LDL、HDL、血UA、血钙等无相关性(P>0.05)。结论2型糖尿病患者25(OH)D缺乏与不足普遍存在,女性患者缺乏更明显。2型糖尿病患者25(OH)D水平与空腹胰岛素呈正相关,与HbA1c、尿微量白蛋白、尿白蛋白肌酐比值呈负相关,25(OH)D缺乏的2型糖尿病患者主要分布在1、2、3、4、11、12月份。
