[ Objective ] According to the theory of blood stasis in traditional Chinese medicine （ TCM）, the animal modeling method of hepatic fibrosis integrated with pathology and symptoms was explored and improved, to const...[ Objective ] According to the theory of blood stasis in traditional Chinese medicine （ TCM）, the animal modeling method of hepatic fibrosis integrated with pathology and symptoms was explored and improved, to construct a new type of rat model of hepatic fibrosis with blood stasis syndrome integrated with tradition- al Chinese and westem medicine. [ Method] The hepatic fibrosis model of blood stasis with blood stasis syndrome was constructed by jointing multi factors, inclu- ding intragastric administration of ethanol, high fat and low protein feeding, joint injection of dimethylnitrosamine （DMN）, bovine serum albumin （BSA） and nor- epinephrine （NE）. The modeling method was further compared with traditional CC14 single-factor modeling method from the aspects of mortality, blood stasis syn- drome of TCM, syndrome grading, general morphology of liver pathology, liver function changes, as well as expression levels of three kinds of collagen （type I and type III collagen, a-SMA） determined by immunohistochemical staining method, and four items of rat hepatic fibrosis （HA, P3NP, LN, CIV content） determined by radio enzyme immunoassay. [ Result ] In blood stasis group, （ 1 ） the mortality of rats was 20% ; （2） model rats appeared typical blood stasis syndromes of TCM such as ecchymosis, dark purple tongue, loose stool, and blood stasis syndrome grading was high; （3） fibrosis changes of liver such as dark white surface, dense gray nodules and brittle texture were observed in general morphological examination; （4） serological liver function tests found that ALT and AST of model rats, as well as TBIL, DBIL and IBIL contents increased significantly; （5） immunohistochemical staining demonstrated that the expression levels of three kinds of collagen （type I and type III collagen, ot-SMA） increased significantly; （6） four items of rat serum hepatic fibrosis, HA, P3NP, LN, CIV content, increased significantly; （7） the above results in blood stasis syndrome model group （except morality and liver function） were higher than those in CC14 modeling group, and the difference was statistically significant （P 〈 0.05 ）. [ Conclusion ] The new improved modeling method effectively reduces high mortality in traditional CC 14 modeling method. In addition to low mortality, the model animal has dual characteristics of disease in western medicine and syndrome in TCM. It is consistent with the pathological characteristics of hepatic fibrosis in western medicine when according with the basic characteristics of blood stasis syndrome in TCM.展开更多
Hepatic fibrosis is a reversible pathological phenomenon in the early and middle stages,but but no satisfactory intervention drugs have been available so far.Recent studies have suggested that microcirculation disturb...Hepatic fibrosis is a reversible pathological phenomenon in the early and middle stages,but but no satisfactory intervention drugs have been available so far.Recent studies have suggested that microcirculation disturbance of liver is one of the important pathogenesis of chronic liver disease,the improvement of microcirculation is beneficial to the recovery of liver function and the delay of liver fibrosis.Hepatic stellate cells are the core cells of hepatic fibrosis,and also the most critical cells that affect the microcirculation of the liver.While TLR4/MyD88/NF-κB and TLR4/MyD88/MAPKs which are based on the action of hepatic stellate cells are two pathways that have very important influence on the inflammatory response of liver,the proliferation and apoptosis of hepatic stellate cells,and the secretion of fibrogenic cytokines.It was found that Plumbapin,the active ingredient of Guangxi specialty ethnic medicine,has the definite effect of promoting blood circulation and removing blood stasis and anti-hepatic fibrosis,but its mechanism is not clear.In this study,the research progress of the above problems was reviewed,and further research ideas were derived as follows:the pharmacological effect of Plumbapin on anti-hepatic fibrosis,promoting blood circulation and removing stasis was based on the influence of TLR4/MyD88/NF-κB and MAPKs signal pathway.展开更多
AIM: To evaluate the effects of varying ischemic durations on cirrhotic liver and to determine the safe upper limit of repeated intermittent hepatic inflow occlusion. METHODS: Hepatic ischemia in cirrhotic rats was in...AIM: To evaluate the effects of varying ischemic durations on cirrhotic liver and to determine the safe upper limit of repeated intermittent hepatic inflow occlusion. METHODS: Hepatic ischemia in cirrhotic rats was induced by clamping the common pedicle of left and median lobes after non-ischemic lobes resection. The cirrhotic rats were divided into six groups according to the duration and form of vascular clamping: sham occlusion (SO), intermittent occlusion for 10 (IO-10), 15(IO-15), 20(IO-20) and 30(IO-30) minutes with 5 minutes of reflow and continuous occlusion for 60 minutes (CO-60). All animals received a total duration of 60 minutes of hepatic inflow occlusion. Liver viability was investigated in relation of hepatic adenylate energy charge (EC). Triphenyltetrazollum chloride (TTC) reduction activities were assayed to qualitatively evaluate the degree of irreversible hepatocellular injury. The biochemical and morphological changes were also assessed and a 7-day mortality was observed. RESULTS: At 60 minutes after reperfusion following a total of 60 minutes of hepatic inflow occlusion, EC values in IO-10 (0.749 +/- 0.012) and IO-15 (0.699 +/- 0.002) groups were rapidly restored to that in SO group (0.748 +/- 0.016), TTC reduction activities remained in high levels (0.144 +/- 0.002 mg/mg protein, 0.139 +/- 0.003 mg/mg protein and 0.121 +/- 0.003 mg/mg protein in SO, IO-10 and IO-15 groups, respectively). But in IO-20 and IO-30 groups, EC levels were partly restored (0.457 +/- 0.023 and 0.534 +/- 0.027) accompanying with a significantly decreased TTC reduction activities (0.070 +/- 0.005 mg/mg protein and 0.061 +/- 0.003 mg/mg protein). No recovery in EC values (0.228 +/- 0.004) and a progressive decrease in TTC reduction activities (0.033 +/- 0.002 mg/mg protein) were shown in CO-60 group. Although not significantly different, the activities of the serum aspartate aminotransferase (AST) on the third postoperative day (POD(3)) and POD(7) and of the serum alanine aminotransferase (ALT) on POD(3) in CO-60 group remained higher than that in intermittent occlusion groups. Moreover, a 60% animal mortality rate and more severe morphological alterations were also shown in CO-60 group. CONCLUSION: Hepatic inflow occlusion during 60 minutes for liver resection in cirrhotic rats resulted in less hepatocellular injury when occlusion was intermittent rather than continuous. Each period of 15 minutes was the safe upper limit of repeated intermittent vascular occlusion that the cirrhotic liver could tolerate without undergoing irreversible hepatocellular injury.展开更多
本实验用四氯化碳(简称 CCl_4)诱发大鼠肝硬化,观察硬化形成过程中门脉和外周血胰岛素的变化,以及门奇静脉断流术后门脉和外周血中胰岛素变化情况。结果发现,随肝硬化程度加重,门静脉压力逐渐增高,门脉血中胰岛素和 C 肽浓度逐渐降低,...本实验用四氯化碳(简称 CCl_4)诱发大鼠肝硬化,观察硬化形成过程中门脉和外周血胰岛素的变化,以及门奇静脉断流术后门脉和外周血中胰岛素变化情况。结果发现,随肝硬化程度加重,门静脉压力逐渐增高,门脉血中胰岛素和 C 肽浓度逐渐降低,外周血胰岛素浓度增高、C 肽浓度减低。断流术前后,门脉和外周血胰岛素和 C 肽浓度、门静脉压力均无明显改变。提示肝硬化时出现的高胰岛素血症主要原因是肝细胞受损,胰岛素降解减少。但断流术能维持门脉血胰岛素的含量,有利于受损肝细胞的恢复和正常肝细胞的再生。展开更多
基金Supported by National Natural Science Foundation of China(81403189,81460628,81660705,81560690)Scientific Research Project of Higher Education in Guangxi Department of Education(YB2014182)
文摘[ Objective ] According to the theory of blood stasis in traditional Chinese medicine （ TCM）, the animal modeling method of hepatic fibrosis integrated with pathology and symptoms was explored and improved, to construct a new type of rat model of hepatic fibrosis with blood stasis syndrome integrated with tradition- al Chinese and westem medicine. [ Method] The hepatic fibrosis model of blood stasis with blood stasis syndrome was constructed by jointing multi factors, inclu- ding intragastric administration of ethanol, high fat and low protein feeding, joint injection of dimethylnitrosamine （DMN）, bovine serum albumin （BSA） and nor- epinephrine （NE）. The modeling method was further compared with traditional CC14 single-factor modeling method from the aspects of mortality, blood stasis syn- drome of TCM, syndrome grading, general morphology of liver pathology, liver function changes, as well as expression levels of three kinds of collagen （type I and type III collagen, a-SMA） determined by immunohistochemical staining method, and four items of rat hepatic fibrosis （HA, P3NP, LN, CIV content） determined by radio enzyme immunoassay. [ Result ] In blood stasis group, （ 1 ） the mortality of rats was 20% ; （2） model rats appeared typical blood stasis syndromes of TCM such as ecchymosis, dark purple tongue, loose stool, and blood stasis syndrome grading was high; （3） fibrosis changes of liver such as dark white surface, dense gray nodules and brittle texture were observed in general morphological examination; （4） serological liver function tests found that ALT and AST of model rats, as well as TBIL, DBIL and IBIL contents increased significantly; （5） immunohistochemical staining demonstrated that the expression levels of three kinds of collagen （type I and type III collagen, ot-SMA） increased significantly; （6） four items of rat serum hepatic fibrosis, HA, P3NP, LN, CIV content, increased significantly; （7） the above results in blood stasis syndrome model group （except morality and liver function） were higher than those in CC14 modeling group, and the difference was statistically significant （P 〈 0.05 ）. [ Conclusion ] The new improved modeling method effectively reduces high mortality in traditional CC 14 modeling method. In addition to low mortality, the model animal has dual characteristics of disease in western medicine and syndrome in TCM. It is consistent with the pathological characteristics of hepatic fibrosis in western medicine when according with the basic characteristics of blood stasis syndrome in TCM.
基金the Research Project of National Natural Science Foundation of China(81960761,81960751,81680705)Basic Ability Improvement Project for Young and Middle-aged Teachers in Colleges and Universities of Guangxi(2018KY1149)Natural Science Foundation of Guangxi Province(2020JJA140257).
文摘Hepatic fibrosis is a reversible pathological phenomenon in the early and middle stages,but but no satisfactory intervention drugs have been available so far.Recent studies have suggested that microcirculation disturbance of liver is one of the important pathogenesis of chronic liver disease,the improvement of microcirculation is beneficial to the recovery of liver function and the delay of liver fibrosis.Hepatic stellate cells are the core cells of hepatic fibrosis,and also the most critical cells that affect the microcirculation of the liver.While TLR4/MyD88/NF-κB and TLR4/MyD88/MAPKs which are based on the action of hepatic stellate cells are two pathways that have very important influence on the inflammatory response of liver,the proliferation and apoptosis of hepatic stellate cells,and the secretion of fibrogenic cytokines.It was found that Plumbapin,the active ingredient of Guangxi specialty ethnic medicine,has the definite effect of promoting blood circulation and removing blood stasis and anti-hepatic fibrosis,but its mechanism is not clear.In this study,the research progress of the above problems was reviewed,and further research ideas were derived as follows:the pharmacological effect of Plumbapin on anti-hepatic fibrosis,promoting blood circulation and removing stasis was based on the influence of TLR4/MyD88/NF-κB and MAPKs signal pathway.
基金This Work was supported by the grant from the Science and Technology Committee of Zhejiang Province,No.971103132
文摘AIM: To evaluate the effects of varying ischemic durations on cirrhotic liver and to determine the safe upper limit of repeated intermittent hepatic inflow occlusion. METHODS: Hepatic ischemia in cirrhotic rats was induced by clamping the common pedicle of left and median lobes after non-ischemic lobes resection. The cirrhotic rats were divided into six groups according to the duration and form of vascular clamping: sham occlusion (SO), intermittent occlusion for 10 (IO-10), 15(IO-15), 20(IO-20) and 30(IO-30) minutes with 5 minutes of reflow and continuous occlusion for 60 minutes (CO-60). All animals received a total duration of 60 minutes of hepatic inflow occlusion. Liver viability was investigated in relation of hepatic adenylate energy charge (EC). Triphenyltetrazollum chloride (TTC) reduction activities were assayed to qualitatively evaluate the degree of irreversible hepatocellular injury. The biochemical and morphological changes were also assessed and a 7-day mortality was observed. RESULTS: At 60 minutes after reperfusion following a total of 60 minutes of hepatic inflow occlusion, EC values in IO-10 (0.749 +/- 0.012) and IO-15 (0.699 +/- 0.002) groups were rapidly restored to that in SO group (0.748 +/- 0.016), TTC reduction activities remained in high levels (0.144 +/- 0.002 mg/mg protein, 0.139 +/- 0.003 mg/mg protein and 0.121 +/- 0.003 mg/mg protein in SO, IO-10 and IO-15 groups, respectively). But in IO-20 and IO-30 groups, EC levels were partly restored (0.457 +/- 0.023 and 0.534 +/- 0.027) accompanying with a significantly decreased TTC reduction activities (0.070 +/- 0.005 mg/mg protein and 0.061 +/- 0.003 mg/mg protein). No recovery in EC values (0.228 +/- 0.004) and a progressive decrease in TTC reduction activities (0.033 +/- 0.002 mg/mg protein) were shown in CO-60 group. Although not significantly different, the activities of the serum aspartate aminotransferase (AST) on the third postoperative day (POD(3)) and POD(7) and of the serum alanine aminotransferase (ALT) on POD(3) in CO-60 group remained higher than that in intermittent occlusion groups. Moreover, a 60% animal mortality rate and more severe morphological alterations were also shown in CO-60 group. CONCLUSION: Hepatic inflow occlusion during 60 minutes for liver resection in cirrhotic rats resulted in less hepatocellular injury when occlusion was intermittent rather than continuous. Each period of 15 minutes was the safe upper limit of repeated intermittent vascular occlusion that the cirrhotic liver could tolerate without undergoing irreversible hepatocellular injury.
文摘本实验用四氯化碳(简称 CCl_4)诱发大鼠肝硬化,观察硬化形成过程中门脉和外周血胰岛素的变化,以及门奇静脉断流术后门脉和外周血中胰岛素变化情况。结果发现,随肝硬化程度加重,门静脉压力逐渐增高,门脉血中胰岛素和 C 肽浓度逐渐降低,外周血胰岛素浓度增高、C 肽浓度减低。断流术前后,门脉和外周血胰岛素和 C 肽浓度、门静脉压力均无明显改变。提示肝硬化时出现的高胰岛素血症主要原因是肝细胞受损,胰岛素降解减少。但断流术能维持门脉血胰岛素的含量,有利于受损肝细胞的恢复和正常肝细胞的再生。
