乳黄制剂对肝硬化大鼠肠源性内毒素血症的研究
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摘要
目的:据统计,大部分的肝硬化病人都合并有肠源性内毒素血症(IETM),大量的内毒素在体内聚集是导致病情恶化的重要原因。在前期防治急性肝性脑病的实验研究中,德高望重的张赤志教授研制出乳黄制剂能显著的降低其血清内毒素的水平。并且陆定波博士在后期的实验研究中通过具体数据的分析得出更确切的结论为:正常组、乳黄制剂预防组、后期乳黄制剂治疗组血清内毒素水平明显低于肝硬化模型组(P＜0.05),且正常组、乳黄制剂预防组、后期乳黄制剂治疗组之间内毒素水平差异无统计学意义(P＞0.05),治疗组与同期治疗对照组之间内毒素水平无明显差异(P＞0.05)。因此,我们的实验将借助肝硬化大鼠模型,从分子水平对乳黄制剂防治肠源性内毒素血症做更深一层的探讨。
方法:1.SPF级雄性wistar大鼠(200～250克)88只,随机分为6组。正常组(n=8)、模型组(n=24)、预防组(n=16)、预防对照组(n=16)、模型治疗组(n=12)、模型治疗对照组(n=12)。
2.除正常组外,其余各组均采用CcL_4复合因素法制造肝硬化模型,饲养10周。
3.造模同时,正常组、模型组予生理盐水按1ml/1100g比例灌胃;预防组、预防对照组在分别给予乳黄制剂、乳果糖也按以上的比例灌胃10周;造模第9周开始分别对模型治疗组、模型治疗对照组按以上比例给予乳黄制剂、乳果糖灌胃连续2周。
4.第10周末将大鼠处死取材。(1)取肝左叶作肝脏组织病理学检测;(2)通过NO检测试剂盒测定各组大鼠血清中NO的含量;(3)用大鼠TNF-α定量酶联检测试剂盒测定肝组织中肿瘤坏死因子含量。
结果:(1)乳黄制剂能改善预防组和模型治疗组肝组织的肝硬化以及纤维组织增生、炎性细胞浸润程度,其中预防组肝组织的病理变化改善最明显。
(2)乳黄制剂可明显降低肝硬化大鼠血清中NO的水平(P＜0.05)。
(3)乳黄制剂可下调肝硬化大鼠肝组织TNF-α的表达水平,从而减少肝脏的直接或间接的伤害。
结论:在实验研究中发现,血清中内毒素的水平与肝脏的炎症反应及肝损害有着明显的正相关。乳黄制剂一方面促进肠道内毒素的排泄,减少肠道中毒素的堆积;一方面酸化肠道,补充肠道的有益菌,平衡肠道微生态环境,提高肠道血流灌注,促进肠细胞增生,减少肠黏膜绒毛上皮脱落变短,降低肠黏膜的通透性,减少内毒素的吸收,使进入血液循环的内毒素明显减少,进而肝组织的炎症反应和肝损害也随之减轻。
Objective:According to statistics,most patients with liver cirrhosis are associated with intestinal endotoxemia(IETM), a large number of endotoxin in vivo aggregation is an important reason for his condition to deteriorate.In the early prevention and treatment of acute hepatic encephalopathy experimental study,the respected Professor Zhang Chizhi Ru Huang preraration found significantly lower serum levels of endotoxin.Dr.Lu Dingbo and experimental research in the post-specific data through a more precise analysis of the conclusions as follows:normal group,prevention group,serum levels of governance mode endotoxin levels were significantly lower than the liver cirrhosis model group(P＜0.05),and normal group,prevention group,governance mode between the endotoxin level was no significant difference(P＞0.05),treatment group and control group over the same period between the treatment of endotoxin level had no significant difference(P＞0.05). Therefore,we will build on the experimental rat model of liver cirrhosis,from the molecular level control of the milk preparation Huang intestinal endotoxemia done to explore deeper.Therefore,we will build on the experimental rat model of liver cirrhosis,from the molecular level of Ru Huang preraration to combat intestinal endotoxemia further explored.
Methods:1.SPF the level male Wistar big mouse(200-250 grams) 88,divide into 6 groups stochastically.Normal group(n=8), model group(n=24),prevention group(n=16),prevention control group(n=16),model treatment group(n=12),model treatment control group(n=12).
2.Besides the normal group,other each group uses the CcL4 compound factor law manufacture liver cirrhosis model,raises 10 weeks.
3.Makes at the same time the mold,the normal group,the model group give the physiological saline to fill the stomach according to the 1ml/100g proportion;The prevention group,the prevention control group is separately giving the breast Ru Huang preparation,the young fructose also presses above proportion to fill the stomach 10 weeks;Makes the mold 9th week to start separately to the model treatment group,the model treatment control group to give the breast Ru Huang preparation, the young fructose according to above proportion fills the stomach continual 2 weeks.
4.10th weekend big mouse execution selection.(1) takes the liver left leaf to make the liver organization pathology examination;(2) determines in each group of big mouse blood serum through the NO examination reagent box the NO content; (3) Rat TNF-αELISA kit Quantitative determination of liver tissue tumor necrosis factor-content.
Results:(1) Ru Huang preraration can improve the prevention and treatment group model of liver cirrhosis and liver tissue fibrous tissue hyperplasia,the degree of inflammatory cell infiltration,including prevention group the pathological changes in liver tissue to improve the most obvious.
(2) Ru Huang preraration can be significantly reduced in rats with cirrhosis of the level of NO in serum(P＜0.05).
(3) Ru Huang preraration can be reduced cirrhosis of rat liver tissue TNF-αexpression levels,thereby reducing liver injury,directly or indirectly.
Conclusion:In the experimental study found that serum endotoxin levels and liver inflammation and liver damage there was a clear positive correlation.Ru Huang preraration on the one hand,the promotion of intestinal excretion of toxins, reducing the accumulation of toxins in the intestinal tract; on the other hand,acidification of the gut have added intestinal bacteria,gut microflora balance of the environment, improve the intestinal blood perfusion,and promote intestinal cell proliferation to reduce the intestinal mucosal villous epithelial shedding shorter,reducing the permeability of intestinal mucosa,reducing the absorption of endotoxin to enter the blood circulation of endotoxin decreased significantly,and the inflammatory response in liver tissue and liver damage also alleviate.
方法:1.SPF级雄性wistar大鼠(200～250克)88只,随机分为6组。正常组(n=8)、模型组(n=24)、预防组(n=16)、预防对照组(n=16)、模型治疗组(n=12)、模型治疗对照组(n=12)。
2.除正常组外,其余各组均采用CcL_4复合因素法制造肝硬化模型,饲养10周。
3.造模同时,正常组、模型组予生理盐水按1ml/1100g比例灌胃;预防组、预防对照组在分别给予乳黄制剂、乳果糖也按以上的比例灌胃10周;造模第9周开始分别对模型治疗组、模型治疗对照组按以上比例给予乳黄制剂、乳果糖灌胃连续2周。
4.第10周末将大鼠处死取材。(1)取肝左叶作肝脏组织病理学检测;(2)通过NO检测试剂盒测定各组大鼠血清中NO的含量;(3)用大鼠TNF-α定量酶联检测试剂盒测定肝组织中肿瘤坏死因子含量。
结果:(1)乳黄制剂能改善预防组和模型治疗组肝组织的肝硬化以及纤维组织增生、炎性细胞浸润程度,其中预防组肝组织的病理变化改善最明显。
(2)乳黄制剂可明显降低肝硬化大鼠血清中NO的水平(P＜0.05)。
(3)乳黄制剂可下调肝硬化大鼠肝组织TNF-α的表达水平,从而减少肝脏的直接或间接的伤害。
结论:在实验研究中发现,血清中内毒素的水平与肝脏的炎症反应及肝损害有着明显的正相关。乳黄制剂一方面促进肠道内毒素的排泄,减少肠道中毒素的堆积;一方面酸化肠道,补充肠道的有益菌,平衡肠道微生态环境,提高肠道血流灌注,促进肠细胞增生,减少肠黏膜绒毛上皮脱落变短,降低肠黏膜的通透性,减少内毒素的吸收,使进入血液循环的内毒素明显减少,进而肝组织的炎症反应和肝损害也随之减轻。
Objective:According to statistics,most patients with liver cirrhosis are associated with intestinal endotoxemia(IETM), a large number of endotoxin in vivo aggregation is an important reason for his condition to deteriorate.In the early prevention and treatment of acute hepatic encephalopathy experimental study,the respected Professor Zhang Chizhi Ru Huang preraration found significantly lower serum levels of endotoxin.Dr.Lu Dingbo and experimental research in the post-specific data through a more precise analysis of the conclusions as follows:normal group,prevention group,serum levels of governance mode endotoxin levels were significantly lower than the liver cirrhosis model group(P＜0.05),and normal group,prevention group,governance mode between the endotoxin level was no significant difference(P＞0.05),treatment group and control group over the same period between the treatment of endotoxin level had no significant difference(P＞0.05). Therefore,we will build on the experimental rat model of liver cirrhosis,from the molecular level control of the milk preparation Huang intestinal endotoxemia done to explore deeper.Therefore,we will build on the experimental rat model of liver cirrhosis,from the molecular level of Ru Huang preraration to combat intestinal endotoxemia further explored.
Methods:1.SPF the level male Wistar big mouse(200-250 grams) 88,divide into 6 groups stochastically.Normal group(n=8), model group(n=24),prevention group(n=16),prevention control group(n=16),model treatment group(n=12),model treatment control group(n=12).
2.Besides the normal group,other each group uses the CcL4 compound factor law manufacture liver cirrhosis model,raises 10 weeks.
3.Makes at the same time the mold,the normal group,the model group give the physiological saline to fill the stomach according to the 1ml/100g proportion;The prevention group,the prevention control group is separately giving the breast Ru Huang preparation,the young fructose also presses above proportion to fill the stomach 10 weeks;Makes the mold 9th week to start separately to the model treatment group,the model treatment control group to give the breast Ru Huang preparation, the young fructose according to above proportion fills the stomach continual 2 weeks.
4.10th weekend big mouse execution selection.(1) takes the liver left leaf to make the liver organization pathology examination;(2) determines in each group of big mouse blood serum through the NO examination reagent box the NO content; (3) Rat TNF-αELISA kit Quantitative determination of liver tissue tumor necrosis factor-content.
Results:(1) Ru Huang preraration can improve the prevention and treatment group model of liver cirrhosis and liver tissue fibrous tissue hyperplasia,the degree of inflammatory cell infiltration,including prevention group the pathological changes in liver tissue to improve the most obvious.
(2) Ru Huang preraration can be significantly reduced in rats with cirrhosis of the level of NO in serum(P＜0.05).
(3) Ru Huang preraration can be reduced cirrhosis of rat liver tissue TNF-αexpression levels,thereby reducing liver injury,directly or indirectly.
Conclusion:In the experimental study found that serum endotoxin levels and liver inflammation and liver damage there was a clear positive correlation.Ru Huang preraration on the one hand,the promotion of intestinal excretion of toxins, reducing the accumulation of toxins in the intestinal tract; on the other hand,acidification of the gut have added intestinal bacteria,gut microflora balance of the environment, improve the intestinal blood perfusion,and promote intestinal cell proliferation to reduce the intestinal mucosal villous epithelial shedding shorter,reducing the permeability of intestinal mucosa,reducing the absorption of endotoxin to enter the blood circulation of endotoxin decreased significantly,and the inflammatory response in liver tissue and liver damage also alleviate.
引文
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