醒腦靜對A型肝性腦病大鼠肝功能、內(nèi)毒素及GS、NOS表達影響的研究
發(fā)布時間：2018-09-18 19:42
【摘要】：研究背景與目的： 目前肝性腦病發(fā)生機理尚未完全明了，治療也無特效療法，危害極大，長期以來一直是國內(nèi)外中西醫(yī)研究的對象。A型肝性腦(Aepatic Encephalopathy ofType A，AHE)病死率高達80%以上，為臨床較為常見的急危重癥。醒腦靜注射液能縮短肝性腦病昏迷時間，促進清醒，有明確的臨床療效。但現(xiàn)有臨床療效觀察資料非常有限，且入選病例較少，缺乏有力的臨床數(shù)據(jù)支持醒腦靜用于治療AHE。 本研究探討300mg·kg-1·d-1的硫代乙酰胺（Thioacetamide，TAA）誘導大鼠A型肝性腦病的造模最適時間；探討醒腦靜對A型肝性腦病大鼠肝功能、內(nèi)毒素及谷氨酰胺合成酶（Glutamine Synthetase，GS）、一氧化氮合酶（Nitric OxideSynthase，NOS）表達的影響。為醒腦靜治療A型肝性腦病提供科學依據(jù)。 方法: 1探討TAA（300mg·kg-1·d-1）誘導大鼠A型肝性腦病的造模最適時間： (1)將60只大鼠分為A、B、C、D四組，其中A組為正常對照組，用同實驗組用藥量相等的生理鹽水灌胃4天。B、C、D三組為實驗組，分別用TAA（300mg·kg-1·d-1）連續(xù)灌胃2天、3天和4天。 (2)比較各組大鼠行為學變化、大鼠AHE的誘導率和致死率；分析各組給藥結(jié)束24小時后血氨、谷草轉(zhuǎn)氨酶(Glutamic Oxalacetic Transaminase，AST)、谷丙轉(zhuǎn)氨酶(Glutamic-Pyruvic Transaminase，ALT)、總膽紅素(Total Bilirubin，TBIL)的差異；比較各組肝組織形態(tài)學變化。 2探討醒腦靜對A型肝性腦病大鼠肝功能、內(nèi)毒素及GS、NOS表達的影響： (1)將60只大鼠分為A、B、C、D、E、F六組，其中A組為正常對照組；B組為A型肝性腦病模型組；C、D、E、F組為治療組，即分別給予已建立A型肝性腦病模型的大鼠醒腦靜（2.5ml·kg-1·d-1）、醒腦靜（5ml·kg-1·d-1）、醒腦靜（10ml·kg-1·d-1）、門冬氨酸鳥氨酸（2g·kg-1·d-1）治療5天。 (2)比較各組大鼠行為學變化、AST、ALT、TBIL的差異；比較各組大鼠肝組織形態(tài)學變化；檢測分析各組INF-α、內(nèi)毒素及GS、NOS表達量的差異。 結(jié)果： 1TAA（300mg·kg-1·d-1）誘導大鼠A型肝性腦病的造模最適時間： (1) B、C、D實驗組較A組正常組大鼠腦功能分級高（P0.0083)，差異有統(tǒng)計學意義；C、D組較B組大鼠腦功能評分高（P0.0083)，差異有統(tǒng)計學意義。 (2) A組正常組，無AHE誘導大鼠也無死亡大鼠；C、D組較B組誘導率高（P0.0083），差異有統(tǒng)計學意義；D組較B、C組的大鼠致死率高（P0.0083)，差異有統(tǒng)計學意義。 (3) B、C、D實驗組大鼠血氨、AST、ALT、TBIL均顯著高于A組正常組（P0.05)，差異有統(tǒng)計學意義；C、D組血氨、AST、ALT、TBIL均較B組高（P0.05)，差異有統(tǒng)計學意義。 (4) A組大鼠肝組織形態(tài)正常；C、D組肝組織學觀察炎癥侵潤、壞死、纖維化等損害較明顯。 2探討醒腦靜對A型肝性腦病大鼠肝功能、內(nèi)毒素及GS、NOS表達的影響： (1) A組正常組大鼠無行為學改變；C、D、E、F用藥組大鼠行為學改變和腦功能分級均較B組低（P0.0033)，差異有統(tǒng)計學意義。 (2) B、C、 D、E、F組大鼠血氨、AST、ALT、TBIL均較A組正常組高（P0.05)，差異有統(tǒng)計學意義；C、 D、E、F組大鼠血氨、AST、ALT、TBIL均較B組有不同程度的降低（P0.05），差異有統(tǒng)計學意義；E組血氨較C組低（P0.05），差異有統(tǒng)計學意義。 (3) A組大鼠肝組織形態(tài)正常；E組肝組織形態(tài)變化較C、D、F組輕，為少量炎癥侵潤，有點狀及少量灶狀壞死，部分肝細胞腫脹.。 (4) B、C、D、E、F組均較A組正常組大鼠INF-α和內(nèi)毒素濃度高（P0.05），差異有統(tǒng)計學意義；E組INF-α和內(nèi)毒素濃度均低于C、 D組（P0.05），差異有統(tǒng)計學意義。 (5) B、C、 D、E、F組均較A組正常組大鼠GS、NOS表達量低（P0.05），差異有統(tǒng)計學意義；E組較C、D組GS表達量較低（P0.05），差異有統(tǒng)計學意義；C、D、E、F組GS、NOS表達量均較B組低（P0.05），差異有統(tǒng)計學意義；D、E、F組較C組NOS表達量低（P0.05），差異有統(tǒng)計學意義。 結(jié)論： 1300mg·kg-1·d-1的TAA連續(xù)灌胃3天為誘導大鼠急性肝性腦病適宜時間。大鼠行為學改變顯著、肝功能損害大、肝組織壞死較嚴重、有較高誘導率及較低致死率。 2A型肝性腦病大鼠通過醒腦靜注射液或門冬氨酸鳥氨酸注射液治療，可改善大鼠行為學變化及肝功能，，減少肝細胞炎癥侵潤及壞死，降低細胞炎癥，降低血液中內(nèi)毒素和INF-α水平，降低腦內(nèi)GS和NOS的表達量。在不同劑量醒腦靜治療中，以10ml·kg-1·d-1的醒腦靜治療綜合效果較好。
[Abstract]:Background and purpose:
At present, the pathogenesis of hepatic encephalopathy has not been fully understood, and there is no specific therapy for it. It is harmful for a long time. It has been studied by Chinese and Western medicine both at home and abroad. However, the available clinical observation data are very limited, and fewer cases are enrolled. There is a lack of strong clinical data to support Xingnaojing in the treatment of AHE.
The aim of this study was to investigate the optimal time for the establishment of hepatic encephalopathy model induced by thioacetamide (TAA) of 300mg 65 To provide scientific basis for the treatment of type A hepatic encephalopathy.
Method:
1 to explore the optimal time of TAA (300mg. Kg-1. D-1) to induce A type hepatic encephalopathy in rats.
(1) Sixty rats were divided into four groups: A, B, C and D. Group A was the normal control group. Group B, C and D were given saline of the same dosage for 4 days. Group B, C and D were given TAA for 2, 3 and 4 days respectively.
(2) To compare the behavioral changes, the induction rate and lethality of AHE, the blood ammonia, glutamic oxalate transaminase (AST), glutamic-Pyruvic transaminase (ALT) and total bilirubin (TBIL) levels 24 hours after the end of administration in each group. Change.
2 to explore the effects of Xingnaojing on liver function, endotoxin, GS and NOS expression in rats with A hepatic encephalopathy.
(1) Sixty rats were divided into six groups: A, B, C, D, E and F, in which group A was the normal control group, group B was the hepatic encephalopathy model group, and group C, D, E and F was the treatment group, which were given Xingnaojing (2.5ml.kg-1.d-1), Xingnaojing (5ml.kg-1.d-1), Xingnaojing (10ml.kg-1.d-1), ornithine aspartate (2g.kg-1.d-1.d-1), respectively. -1) for 5 days.
(2) Comparing the behavioral changes, the differences of AST, ALT and TBIL, the morphological changes of liver tissues, and the expression of INF-alpha, endotoxin, GS and NOS in each group.
Result:
The optimal time for 1TAA (300mg. Kg-1. D-1) to induce A type hepatic encephalopathy in rats:
(1) The brain function grading of B, C, D experimental group was higher than that of A normal group (P 0.0083), the difference was statistically significant; the brain function score of C, D experimental group was higher than that of B experimental group (P 0.0083), the difference was statistically significant.
(2) Normal group A, no AHE-induced rats and no death rats; C, D group than B group induced rate higher (P 0.0083), the difference was statistically significant; D group than B, C group rats mortality higher (P 0.0083), the difference was statistically significant.
(3) The serum ammonia, AST, ALT and TBIL of rats in group B, C and D were significantly higher than those in group A (P 0.05), and the differences were statistically significant.
(4) The morphology of liver tissue in group A was normal, and the liver histology in group C and D showed obvious damage of inflammation, invasion, necrosis and fibrosis.
2 to explore the effects of Xingnaojing on liver function, endotoxin, GS and NOS expression in rats with A hepatic encephalopathy.
(1) There were no behavioral changes in normal rats in group A, and the behavioral changes and brain function grading of rats in group C, D, E and F were lower than those in group B (P 0.0033).
(2) The levels of serum ammonia, AST, ALT and TBIL in group B, C, D, E and F were higher than those in group A (P 0.05), and the difference was statistically significant; the levels of serum ammonia, AST, ALT and TBIL in group C, D, E and F were lower than those in group B (P 0.05), and the difference was statistically significant.
(3) The morphology of liver tissue in group A was normal; the morphological changes of liver tissue in group E were slighter than those in group C, D and F, with a small amount of inflammation and invasion, a small amount of focal necrosis, and some hepatocytes swelling.
(4) The concentrations of INF-a and endotoxin in group B, C, D, E and F were higher than those in group A (P 0.05), and the differences were statistically significant. The concentrations of INF-a and endotoxin in group E were lower than those in group C and D (P 0.05).
(5) The expression of GS and NOS in group B, C, D, E and F was lower than that in group A (P 0.05), and the difference was statistically significant; the expression of GS and NOS in group E was lower than that in group C and D (P 0.05), and the difference was statistically significant; the expression of GS and NOS in group C, D, E, F was lower than that in group B (P 0.05), and the expression of NOS in group D, E, F was lower than that in group C (P 0.05).
Conclusion:
The suitable time for inducing acute hepatic encephalopathy was 3 days of continuous administration of TAA at 1300 mg kg 1 D 1. The behavior of the rats was significantly changed, the liver function was damaged, the necrosis of liver tissue was serious, the inducing rate was high and the mortality was low.
Xingnaojing injection or ornithine Aspartate Injection can improve the behavioral changes and liver function of rats with hepatic encephalopathy type 2A, reduce inflammation, invasion and necrosis of hepatocytes, reduce inflammation of hepatocytes, reduce the levels of endotoxin and INF-alpha in blood, and decrease the expression of GS and NOS in brain. Xingnaojing treatment of L. Kg-1 D-1 has a good comprehensive effect.
【學位授予單位】：廣州醫(yī)科大學
【學位級別】：碩士
【學位授予年份】：2014
【分類號】：R747.9
本文編號：2248932
[Abstract]:Background and purpose:
At present, the pathogenesis of hepatic encephalopathy has not been fully understood, and there is no specific therapy for it. It is harmful for a long time. It has been studied by Chinese and Western medicine both at home and abroad. However, the available clinical observation data are very limited, and fewer cases are enrolled. There is a lack of strong clinical data to support Xingnaojing in the treatment of AHE.
The aim of this study was to investigate the optimal time for the establishment of hepatic encephalopathy model induced by thioacetamide (TAA) of 300mg 65 To provide scientific basis for the treatment of type A hepatic encephalopathy.
Method:
1 to explore the optimal time of TAA (300mg. Kg-1. D-1) to induce A type hepatic encephalopathy in rats.
(1) Sixty rats were divided into four groups: A, B, C and D. Group A was the normal control group. Group B, C and D were given saline of the same dosage for 4 days. Group B, C and D were given TAA for 2, 3 and 4 days respectively.
(2) To compare the behavioral changes, the induction rate and lethality of AHE, the blood ammonia, glutamic oxalate transaminase (AST), glutamic-Pyruvic transaminase (ALT) and total bilirubin (TBIL) levels 24 hours after the end of administration in each group. Change.
2 to explore the effects of Xingnaojing on liver function, endotoxin, GS and NOS expression in rats with A hepatic encephalopathy.
(1) Sixty rats were divided into six groups: A, B, C, D, E and F, in which group A was the normal control group, group B was the hepatic encephalopathy model group, and group C, D, E and F was the treatment group, which were given Xingnaojing (2.5ml.kg-1.d-1), Xingnaojing (5ml.kg-1.d-1), Xingnaojing (10ml.kg-1.d-1), ornithine aspartate (2g.kg-1.d-1.d-1), respectively. -1) for 5 days.
(2) Comparing the behavioral changes, the differences of AST, ALT and TBIL, the morphological changes of liver tissues, and the expression of INF-alpha, endotoxin, GS and NOS in each group.
Result:
The optimal time for 1TAA (300mg. Kg-1. D-1) to induce A type hepatic encephalopathy in rats:
(1) The brain function grading of B, C, D experimental group was higher than that of A normal group (P 0.0083), the difference was statistically significant; the brain function score of C, D experimental group was higher than that of B experimental group (P 0.0083), the difference was statistically significant.
(2) Normal group A, no AHE-induced rats and no death rats; C, D group than B group induced rate higher (P 0.0083), the difference was statistically significant; D group than B, C group rats mortality higher (P 0.0083), the difference was statistically significant.
(3) The serum ammonia, AST, ALT and TBIL of rats in group B, C and D were significantly higher than those in group A (P 0.05), and the differences were statistically significant.
(4) The morphology of liver tissue in group A was normal, and the liver histology in group C and D showed obvious damage of inflammation, invasion, necrosis and fibrosis.
2 to explore the effects of Xingnaojing on liver function, endotoxin, GS and NOS expression in rats with A hepatic encephalopathy.
(1) There were no behavioral changes in normal rats in group A, and the behavioral changes and brain function grading of rats in group C, D, E and F were lower than those in group B (P 0.0033).
(2) The levels of serum ammonia, AST, ALT and TBIL in group B, C, D, E and F were higher than those in group A (P 0.05), and the difference was statistically significant; the levels of serum ammonia, AST, ALT and TBIL in group C, D, E and F were lower than those in group B (P 0.05), and the difference was statistically significant.
(3) The morphology of liver tissue in group A was normal; the morphological changes of liver tissue in group E were slighter than those in group C, D and F, with a small amount of inflammation and invasion, a small amount of focal necrosis, and some hepatocytes swelling.
(4) The concentrations of INF-a and endotoxin in group B, C, D, E and F were higher than those in group A (P 0.05), and the differences were statistically significant. The concentrations of INF-a and endotoxin in group E were lower than those in group C and D (P 0.05).
(5) The expression of GS and NOS in group B, C, D, E and F was lower than that in group A (P 0.05), and the difference was statistically significant; the expression of GS and NOS in group E was lower than that in group C and D (P 0.05), and the difference was statistically significant; the expression of GS and NOS in group C, D, E, F was lower than that in group B (P 0.05), and the expression of NOS in group D, E, F was lower than that in group C (P 0.05).
Conclusion:
The suitable time for inducing acute hepatic encephalopathy was 3 days of continuous administration of TAA at 1300 mg kg 1 D 1. The behavior of the rats was significantly changed, the liver function was damaged, the necrosis of liver tissue was serious, the inducing rate was high and the mortality was low.
Xingnaojing injection or ornithine Aspartate Injection can improve the behavioral changes and liver function of rats with hepatic encephalopathy type 2A, reduce inflammation, invasion and necrosis of hepatocytes, reduce inflammation of hepatocytes, reduce the levels of endotoxin and INF-alpha in blood, and decrease the expression of GS and NOS in brain. Xingnaojing treatment of L. Kg-1 D-1 has a good comprehensive effect.
【學位授予單位】：廣州醫(yī)科大學
【學位級別】：碩士
【學位授予年份】：2014
【分類號】：R747.9
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