脂肝方对非酒精性脂肪肝大鼠中脂联素抵抗素影响研究
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摘要
目的
中药复方“脂肝方”是导师周福生教授的经验方,经过多年临床观察其对脾虚痰瘀型非酒精性脂肪肝患者能明显改善临床症状,并有调节血脂代谢,改善肝功能且未有不良反应。本课题试图通过建立非酒精性脂肪肝大鼠模型来探讨中药复方“脂肝方”对脂联素及抵抗素表达量影响的可能作用机制。
方法
将48只SD大鼠适应性喂养1周后随机分出8只(采标本麻醉过量死亡1只)作为正常对照组,其余40只参照范建高教授予高脂饲料(2%胆固醇+10%猪油+88%标准饲料)喂养8周复制非酒精性脂肪肝大鼠模型、12周复制脂肪性肝炎大鼠模型后,随机分出8只模型组(不给予任何药物),将余下32只成功造模的脂肪性肝炎大鼠随机分为中药复方“脂肝方”高剂量组8只、中剂量组8只及低剂量组8只,和西药立普妥对照组8只。实验于第16周末注射麻醉,取出肝脏,在肝脏右叶中部的肝组织10%甲醛固定5天,脱水包埋切片、HE染色,光镜下观察。运用ELISA法检测血浆脂联素、抵抗素浓度。
结果
(1)在喂养期间,正常组体重上升缓慢,实验造模组大鼠体重增加较为明显。与正常组体重比较,模型组P<0.05,差异有统计学意义。与模型组比较,西药组、中药高、中、低剂量组比较P>0.05,差异无统计学意义。(2)与正常组大鼠肝重比较,模型组P<0.05,差异有统计学意义；与模型组比较,西药组、中药高、中、低剂量组比较P>0.05,差异无统计学意义。经相关性分析表明,大鼠体重与其肝脏重量存在线性正相关性。(3)光镜下观察大鼠肝小叶内含脂滴细胞数／总细胞数,与正常组比较,模型组P<0.05,差异均有统计学意义。与模型组比较,除西药组以外,中药高、中、低剂量组比较P<0.05,差异有统计学意义；与中药低剂量组比较,中药高、中剂量组P<0.05差异均有统计学意义；与中药中剂量组比较,中药高剂量组P<0.05,差异有统计学意义,低剂量组P>0.05,差异无统计学意义。(4)与模型组比较,在改善肝内炎症活动度方面,除西药组外,其余各组均P<0.05,差异有统计学意义。(5)在实验中,西药组和中药高、中、低剂量组均可增加脂联素的表达量。与正常组脂联素比较,模型组P<0.05,差异有统计学意义；与模型组比较,西药组、中药高、中、低剂量组均P<0.05,差异有统计学意义；与西药组比较,中药低剂量组P<0.05,差异有统计学意义；高中剂量组比较P>0.05,差异无统计学意义。(6)在实验中,西药组和中药高、中、低剂量组均可降低抵抗素的表达量,与正常组抵抗素比较,模型组P<0.05,差异有统计学意义；与模型组比较,西药组、中药高、中、低剂量组均P<0.05,差异有统计学意义；与西药组比较,模型组、中药中、低剂量组均P<0.05,差异有统计学意义；高剂量组P>0.05,差异无统计学意义。与中药低剂量组比较,中药中、高剂量组P>0.05,差异无统计学意义。
结论
(1)脂联素、抵抗素与非酒精性脂肪肝发病密切相关。(2)中药复方“脂肝方”有效改善肝内炎症活动度及增加脂联素、降低抵抗素表达量。(3)中药复方“脂肝方”是治疗非酒精性脂肪肝的有效方剂。其作用机制部分可能与影响脂联素抵抗素有关。
Objective
Chinese herbal formula "zhiganfang" is the experience prescription of Professor Zhou Fusheng, After many years for clinical observation, we can find that Chinese herbal formula "zhiganfang" can significantly improve the clinical symptoms of NAFLD, it can regulate metabolism of TG, improve liver function and no adverse reactions. This topic attempts to discuss the possible mechanism of adiponectin and resistin for Chinese herbal formula "zhiganfang" by establishing non-alcoholic fatty liver rat model.
Methods
48 SD rats were randomly divided into a control group (one death in collected samples causing by narcotic overdose), of which 12 weeks of high fat diet rat NASH model, after the success of stochastic modeling, separation 8 of model group, the 32 successful model of SD rats were randomly into "zhiganfang" high dose group, middle dose group, low dose group and western medicine control group. ELISA assay for resistin and adiponectin.
Results
(1) body weight compared with normal group, model group P<0.05, the difference was statis-tically significant; with the model group, western medicine group, "zhiganfang" high, medium and low groups were P>0.05, the difference was not statistically significant. (2) liver weight in rats compared with normal group P<0.05, the difference was statis-tically significant; with the model group, western medicine group, "zhiganfang" high, medium and low groups were P>0.05, the difference was not statistically significant.The correlation analysis showed that it was linear correlation between the liver weight and body weight of rats (3) light microscopy of lipid droplets containing rat hepatic lobule cells/total cell number, compared with normal group, model group P<0.05, the difference was statis-tically significant. Compared with model group, rats in each group were significant differences (P<0.05)except Western medicine group; Compared with the "zhiganfang" low dose group, " zhiganfang " high dose group P<0.05,the differences were Statistical significance; and compared with "zhiganfang" middle dose group, "zhiganfang" high group P<0.05, the differences were Statistical significance. And low dose group P>0.05, the difference was not statistically significant. (4)compared with model group, in addition to Western medicine group, the other rats in each group differences in liver inflammation were significant (P<0.05). (5) plasma Adiponectin:compared with normal group, model group P<0.05, the difference was statis-tically significant compared with model group; compared with the model group, western medicine group, "zhiganfang" high, medium and low dose groups were P<0.05, the differences were Statistical significance; compared with western medicine group, "zhiganfang"low dose group were P<0.05, there were significant difference; "zhiganfang" high dose group, middle dose group, P>0.05, the difference was not statistically significant. (6) Plasma Resistin:compared with normal group, model group P<0.05, the difference was statis-tically significant compared with model group;Compared with the model group, western medicine group, "zhiganfang" high, medium and low dose groups were P<0.05, there were significant difference;Compared western medicine group, the "zhiganfang" low and medium dose group was P<0.05, there was significant difference; "zhiganfang" high-dose group, P>0.05, the difference was not statistically significant.; Compared with "zhiganfang" low dose group, medium and high dose group P>0.05, the difference was not statistically significant.
Conclusions
(1)Adiponectin and resistin are closely related to non-alcoholic fatty liver disease. (2) "zhiganfang" can improve lipid droplets in rat hepatic lobule containing cells/total cells, and it also can increase Adiponectin expression and decrease the expression of Resistin. (3) Chinese herbal formula "zhiganfang " is an effective prescription for the treatment of non-alcoholic fatty liver. Part of the mechanism may be related to adiponectin and resistin.
中药复方“脂肝方”是导师周福生教授的经验方,经过多年临床观察其对脾虚痰瘀型非酒精性脂肪肝患者能明显改善临床症状,并有调节血脂代谢,改善肝功能且未有不良反应。本课题试图通过建立非酒精性脂肪肝大鼠模型来探讨中药复方“脂肝方”对脂联素及抵抗素表达量影响的可能作用机制。
方法
将48只SD大鼠适应性喂养1周后随机分出8只(采标本麻醉过量死亡1只)作为正常对照组,其余40只参照范建高教授予高脂饲料(2%胆固醇+10%猪油+88%标准饲料)喂养8周复制非酒精性脂肪肝大鼠模型、12周复制脂肪性肝炎大鼠模型后,随机分出8只模型组(不给予任何药物),将余下32只成功造模的脂肪性肝炎大鼠随机分为中药复方“脂肝方”高剂量组8只、中剂量组8只及低剂量组8只,和西药立普妥对照组8只。实验于第16周末注射麻醉,取出肝脏,在肝脏右叶中部的肝组织10%甲醛固定5天,脱水包埋切片、HE染色,光镜下观察。运用ELISA法检测血浆脂联素、抵抗素浓度。
结果
(1)在喂养期间,正常组体重上升缓慢,实验造模组大鼠体重增加较为明显。与正常组体重比较,模型组P<0.05,差异有统计学意义。与模型组比较,西药组、中药高、中、低剂量组比较P>0.05,差异无统计学意义。(2)与正常组大鼠肝重比较,模型组P<0.05,差异有统计学意义；与模型组比较,西药组、中药高、中、低剂量组比较P>0.05,差异无统计学意义。经相关性分析表明,大鼠体重与其肝脏重量存在线性正相关性。(3)光镜下观察大鼠肝小叶内含脂滴细胞数／总细胞数,与正常组比较,模型组P<0.05,差异均有统计学意义。与模型组比较,除西药组以外,中药高、中、低剂量组比较P<0.05,差异有统计学意义；与中药低剂量组比较,中药高、中剂量组P<0.05差异均有统计学意义；与中药中剂量组比较,中药高剂量组P<0.05,差异有统计学意义,低剂量组P>0.05,差异无统计学意义。(4)与模型组比较,在改善肝内炎症活动度方面,除西药组外,其余各组均P<0.05,差异有统计学意义。(5)在实验中,西药组和中药高、中、低剂量组均可增加脂联素的表达量。与正常组脂联素比较,模型组P<0.05,差异有统计学意义；与模型组比较,西药组、中药高、中、低剂量组均P<0.05,差异有统计学意义；与西药组比较,中药低剂量组P<0.05,差异有统计学意义；高中剂量组比较P>0.05,差异无统计学意义。(6)在实验中,西药组和中药高、中、低剂量组均可降低抵抗素的表达量,与正常组抵抗素比较,模型组P<0.05,差异有统计学意义；与模型组比较,西药组、中药高、中、低剂量组均P<0.05,差异有统计学意义；与西药组比较,模型组、中药中、低剂量组均P<0.05,差异有统计学意义；高剂量组P>0.05,差异无统计学意义。与中药低剂量组比较,中药中、高剂量组P>0.05,差异无统计学意义。
结论
(1)脂联素、抵抗素与非酒精性脂肪肝发病密切相关。(2)中药复方“脂肝方”有效改善肝内炎症活动度及增加脂联素、降低抵抗素表达量。(3)中药复方“脂肝方”是治疗非酒精性脂肪肝的有效方剂。其作用机制部分可能与影响脂联素抵抗素有关。
Objective
Chinese herbal formula "zhiganfang" is the experience prescription of Professor Zhou Fusheng, After many years for clinical observation, we can find that Chinese herbal formula "zhiganfang" can significantly improve the clinical symptoms of NAFLD, it can regulate metabolism of TG, improve liver function and no adverse reactions. This topic attempts to discuss the possible mechanism of adiponectin and resistin for Chinese herbal formula "zhiganfang" by establishing non-alcoholic fatty liver rat model.
Methods
48 SD rats were randomly divided into a control group (one death in collected samples causing by narcotic overdose), of which 12 weeks of high fat diet rat NASH model, after the success of stochastic modeling, separation 8 of model group, the 32 successful model of SD rats were randomly into "zhiganfang" high dose group, middle dose group, low dose group and western medicine control group. ELISA assay for resistin and adiponectin.
Results
(1) body weight compared with normal group, model group P<0.05, the difference was statis-tically significant; with the model group, western medicine group, "zhiganfang" high, medium and low groups were P>0.05, the difference was not statistically significant. (2) liver weight in rats compared with normal group P<0.05, the difference was statis-tically significant; with the model group, western medicine group, "zhiganfang" high, medium and low groups were P>0.05, the difference was not statistically significant.The correlation analysis showed that it was linear correlation between the liver weight and body weight of rats (3) light microscopy of lipid droplets containing rat hepatic lobule cells/total cell number, compared with normal group, model group P<0.05, the difference was statis-tically significant. Compared with model group, rats in each group were significant differences (P<0.05)except Western medicine group; Compared with the "zhiganfang" low dose group, " zhiganfang " high dose group P<0.05,the differences were Statistical significance; and compared with "zhiganfang" middle dose group, "zhiganfang" high group P<0.05, the differences were Statistical significance. And low dose group P>0.05, the difference was not statistically significant. (4)compared with model group, in addition to Western medicine group, the other rats in each group differences in liver inflammation were significant (P<0.05). (5) plasma Adiponectin:compared with normal group, model group P<0.05, the difference was statis-tically significant compared with model group; compared with the model group, western medicine group, "zhiganfang" high, medium and low dose groups were P<0.05, the differences were Statistical significance; compared with western medicine group, "zhiganfang"low dose group were P<0.05, there were significant difference; "zhiganfang" high dose group, middle dose group, P>0.05, the difference was not statistically significant. (6) Plasma Resistin:compared with normal group, model group P<0.05, the difference was statis-tically significant compared with model group;Compared with the model group, western medicine group, "zhiganfang" high, medium and low dose groups were P<0.05, there were significant difference;Compared western medicine group, the "zhiganfang" low and medium dose group was P<0.05, there was significant difference; "zhiganfang" high-dose group, P>0.05, the difference was not statistically significant.; Compared with "zhiganfang" low dose group, medium and high dose group P>0.05, the difference was not statistically significant.
Conclusions
(1)Adiponectin and resistin are closely related to non-alcoholic fatty liver disease. (2) "zhiganfang" can improve lipid droplets in rat hepatic lobule containing cells/total cells, and it also can increase Adiponectin expression and decrease the expression of Resistin. (3) Chinese herbal formula "zhiganfang " is an effective prescription for the treatment of non-alcoholic fatty liver. Part of the mechanism may be related to adiponectin and resistin.
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