胆固醇代谢紊乱SD大鼠肝细胞膜生物泵糠蛋白表达的平行对照分析
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摘要
目的分析胆固醇代谢紊乱的SD大鼠肝细胞膜生物泵糖蛋白(Pgp)及相关生化指标与正常大鼠的差异性。方法选取SD大鼠30只,随机均分为对照组与观察组,每组各15只;观察组大鼠以高脂饲料喂养法制备为胆固醇代谢紊乱模型,对照组大鼠常规喂养保持健康;以免疫组化法分析两组大鼠肝脏Pgp表达水平并进行比较,同时比较两组大鼠肝匀浆的各项相关生化指标。结果对照组大鼠肝脏Pgp平均光度值为(1.01±0.13),肝指数为(1.69±0.68);观察组大鼠肝脏Pgp平均光度值为(5.36±1.21),肝指数(3.35±0.37);观察组肝脏Pgp平均光度值与肝指数均显著高于对照组(P<0.01)。观察组肝脏脂肪病变+++的发生率为53.33%,对照组无+++级别肝脏脂肪病变发生,观察组整体肝脏脂肪病变程度较对照组严重(P<0.01)。观察组与对照组大鼠初始体质量、肝匀浆TBA,差异无统计学意义(P>0.05);观察组与对照组大鼠血清Tch比较差异有统计学意义(P<0.05);两组其他各项指标均差异具有统计学意义(P<0.01)。肝脏脂肪病变程度与肝脏Pgp光度值呈显著高度正相关性,0.8肝细胞膜生物泵糖蛋白表达显著高于健康大鼠,提示肝脏Pgp过高表达在胆固醇代谢紊乱的发生发展过程中发挥着重要作用,应引起胆固醇代谢紊乱防治研究的关注。
Objective To analyze the difference of Biological pump glycoprotein(Pgp) of SD rat liver cell membrane with cholesterol metabolism disorder and its related biochemical indexes and the normal rats. Methods 30 SD rats were selected and randomly divided into observation group and control group,15 rats in each group.The rats in observation group fed with high fat diet were prepared for the disorder of cholesterol metabolism in model,and rats of control group fed healthy.Immunohistochemical method was used to analyze the expression of Pgp in two groups of rats. And they were compared.The related biochemical indexes of rat liver homogenate of the two groups were also compared. Results The average Pgp value of rat liver of control group was(1.01±0.13),the liver index was(1.69±0.68).The average Pgp value of rat liver of observation group was(5.36±1.21),the liver index was(3.35±0.37).The average Pgp value of rat liver and liver index in observation group group were significantly higher than those of control group(P < 0.01).The hepatic steatosis +++ incidence rate of observation group was 53.33%,the control group had no pathological changes of liver fat level +++.The observation group overall hepatic steatosis degree was more serious than the control group,(P < 0.01).There were no statistical differences on rats initial body weight and liver homogenate TBA between the observation group and the control group(P > 0.05).There was some statistical difference on rats serum Tch between observation group and control group(P < 0.05).The other indexes showed statistically significant differences,(P < 0.01).There was a significant positive correlation between the degree of hepatic steatosis and Pgp value of liver,0.8 < r < 1,P < 0.01. Conclusion The liver cell membrane glycoprotein biological pump cholesterol metabolism in SD rats is significantly higher than that of healthy rats,which suggests that liver Pgp overexpression plays an important role in the occurrence and development of cholesterol metabolism.It should be on the prevention and treatment of cholesterol metabolism in attention.
Objective To analyze the difference of Biological pump glycoprotein(Pgp) of SD rat liver cell membrane with cholesterol metabolism disorder and its related biochemical indexes and the normal rats. Methods 30 SD rats were selected and randomly divided into observation group and control group,15 rats in each group.The rats in observation group fed with high fat diet were prepared for the disorder of cholesterol metabolism in model,and rats of control group fed healthy.Immunohistochemical method was used to analyze the expression of Pgp in two groups of rats. And they were compared.The related biochemical indexes of rat liver homogenate of the two groups were also compared. Results The average Pgp value of rat liver of control group was(1.01±0.13),the liver index was(1.69±0.68).The average Pgp value of rat liver of observation group was(5.36±1.21),the liver index was(3.35±0.37).The average Pgp value of rat liver and liver index in observation group group were significantly higher than those of control group(P < 0.01).The hepatic steatosis +++ incidence rate of observation group was 53.33%,the control group had no pathological changes of liver fat level +++.The observation group overall hepatic steatosis degree was more serious than the control group,(P < 0.01).There were no statistical differences on rats initial body weight and liver homogenate TBA between the observation group and the control group(P > 0.05).There was some statistical difference on rats serum Tch between observation group and control group(P < 0.05).The other indexes showed statistically significant differences,(P < 0.01).There was a significant positive correlation between the degree of hepatic steatosis and Pgp value of liver,0.8 < r < 1,P < 0.01. Conclusion The liver cell membrane glycoprotein biological pump cholesterol metabolism in SD rats is significantly higher than that of healthy rats,which suggests that liver Pgp overexpression plays an important role in the occurrence and development of cholesterol metabolism.It should be on the prevention and treatment of cholesterol metabolism in attention.
引文
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[14]王凤玲,隋小芳,索树珍,等.胆固醇代谢紊乱及其相关疾病的研究进展[J].中国老年保健医学,2015,13(1):13-15.
[15]李凤霞,李金磊,荣向路,等.脂肪分化障碍引起的胰岛素抵抗、脂肪肝及高胆固醇血症小鼠模型研究[J].中药新药与临床药理,2014,25(1):96-101.
[2]ZHAO Rui-zhi,LIU Li-juan,WANG Yin-jie,et al.Vinegar-baked Radix Bupleuri modulates the cell membrane constituents and inhibits the P-gp activity in rat hepatocytes[J].Complementary and Alternative Medicine,2014,5(14):357.
[3]程志英,李霞,张淑珍,等.二甲双胍对糖尿病大鼠肝脏中重要转运蛋白表达的影响[J].中国药师,2014,17(6):901-903.
[4]汤燕,高巧慧,吴臻,等.P-糖蛋白的细胞内转运及表达调控[J].生命的化学,2014,34(1):93-97.
[5]杜惠惠,任强,刘晓民.P-糖蛋白介导的肿瘤多药耐药机制及其逆转策略[J].中华肺部疾病杂志(电子版),2013,6(6):551-553.
[6]杨雯,周惠芬,杨洁红,等.川芎嗪在Caco-2细胞单层模型的转运特征及对P-糖蛋白表达的影响[J].中草药,2013,44(5):581-585.
[7]萨础拉,吕航,姜艳艳,等.三七皂苷在大鼠外翻肠囊中的吸收及与P-糖蛋白相互作用研究[J].北京中医药大学学报,2011,34(12):836-842.
[8]穆艳飞.IL-6对类风湿关节炎患者外周血淋巴细胞P-糖蛋白的调控研究[D].山西医科大学,2014.
[9]Binkhathlan Z,Lavasanifar A.P-glycoprotein inhibition as a therapeutic approach for overcoming multidrug resistance in cancer:current status and future perspectives[J].Curr Cancer Drug Targets,2013,13(3):326-346.
[10]陈振兴,赵瑞芝.醋柴胡不同部位对肝郁模型大鼠肝脏Na+-K+ATP酶、Ca2+-Mg2+ATP酶活性及P-糖蛋白m RNA表达的影响[J].中华中医药杂志,2016,31(9):3721-3724.
[11]Patel A,Tiwari AK,Chufan EE,et al.PD173074,a selective FGFR inhibitor,reverses ABCB1-mediated drug resistance in cancer cells[J].Cancer Chemother Pharmacol,2013,72(1):189-199.
[12]侯鹏高.动脉粥样硬化与脂代谢紊乱研究进展[J].齐齐哈尔医学院学报,2015,36(7):1039-1040.
[13]康卓颖,初欣欣,杨润梅,等.金黄地鼠高脂血症模型胆固醇代谢紊乱的生物标志物的研究[J].中国药理学通报,2014,30(6):880-883.
[14]王凤玲,隋小芳,索树珍,等.胆固醇代谢紊乱及其相关疾病的研究进展[J].中国老年保健医学,2015,13(1):13-15.
[15]李凤霞,李金磊,荣向路,等.脂肪分化障碍引起的胰岛素抵抗、脂肪肝及高胆固醇血症小鼠模型研究[J].中药新药与临床药理,2014,25(1):96-101.