基于果蝇生物模式的雷公藤甘草配伍改善糖脂代谢紊乱增效减毒研究
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摘要
目的利用高脂、高糖诱导的果蝇糖脂代谢紊乱模型探讨雷公藤甘草配伍增效和减毒作用。方法雄性果蝇随机分组,分别采用高糖、高脂培养基喂养2周,将雷公藤、甘草或雷公藤甘草混合提取物加入相应造模培养基中继续培养2周,测定果蝇体内的海藻糖、甘油三酯、胆固醇水平,评估雷公藤、甘草对糖脂代谢紊乱的改善作用或雷公藤甘草配伍的增效作用;正常培养基持续给药,测定相应的果蝇生存曲线、平均寿命、最高寿命和产卵率评估雷公藤的毒性及甘草配伍雷公藤的减毒作用。结果与模型组比较,雷公藤、甘草均能降低高脂或高糖诱导的果蝇海藻糖水平的升高,甘草对果蝇体内的甘油三酯水平并无显著影响,且甘草配伍后显著增强雷公藤的降糖、降甘油三酯作用,并具有统计学差异;对胆固醇水平的调节作用,雷公藤、甘草分别在高脂、高糖模型中起主导作用,而两者联合明显具有协同作用并具有统计学差异;长期给药甘草配伍雷公藤显著逆转雷公藤引起果蝇生存率、果蝇的平均寿命和最高寿命、产卵量的降低,并具有统计学差异。结论雷公藤和甘草均有一定降脂作用,配伍使用后能够增强降脂活性并有效减少雷公藤的毒性。
Objective To explore the synergia and toxicity attenuated effect of the tripterygium wilfordii cooperated with liquiritia based on the lipid metabolic disturbance mode of the fruit flies induced by high fat and sugar.Methods Male fruit flies were assigned randomly, fed in high sugar and high fat medium for 2 weeks respectively, then the model medium was added tripterygium wilfordii, liquiritia or the mixed extract of them and cultivated for 2 weeks to evaluate the improvement effect of tripterygium wilfordii and liquiritia to glucose and lipid metabolism disorder or the synergy effect of the drug combination by measuring the level of the trehalose, triglyceride and the cholesterol. The control medium was given a continuous dosing, the toxicity of the tripterygium wilfordii or the Synergistic effect of the compatibility with liquiritia was evaluated by measuring the survivorship curve, the average lifetime, the highest lifetime and the spawning rate of the fruit flies.Results Compared with the model group, Tripterygium wilfordii and liquiritia could reduce the level of trehalose induced by high fat or high sugar, with liquiritia having no significant effect on the triglyceride level in the fruit flies,but enhancing the hypoglycemic and triglyceride effect of Tripterygium wilfordi after Compatibility significantly, which had statistical difference.With respect to regulation of cholesterol levels, Tripterygium ilfordii and liquiritia that played a dominant role in the high fat and high sugar models had synergistic effects when they were combined,which had statistical differences. In addition, the long term administration of Tripterygium wilfordii combining with liquiritia significantly reverses the reduction of the survival rate of fruit flies, the average life span of fruit flies, the maximum life span and the decrease of the amount of spawning caused by Tripterygium wilfordii with statistical differences.Conclusion Tripterygium wilfordii and liquiritia have certain lipid-lowering effects, which can enhance the lipid-lowering activity and reduce the toxicity of Tripterygium wilfordii effectively when they were combined.
Objective To explore the synergia and toxicity attenuated effect of the tripterygium wilfordii cooperated with liquiritia based on the lipid metabolic disturbance mode of the fruit flies induced by high fat and sugar.Methods Male fruit flies were assigned randomly, fed in high sugar and high fat medium for 2 weeks respectively, then the model medium was added tripterygium wilfordii, liquiritia or the mixed extract of them and cultivated for 2 weeks to evaluate the improvement effect of tripterygium wilfordii and liquiritia to glucose and lipid metabolism disorder or the synergy effect of the drug combination by measuring the level of the trehalose, triglyceride and the cholesterol. The control medium was given a continuous dosing, the toxicity of the tripterygium wilfordii or the Synergistic effect of the compatibility with liquiritia was evaluated by measuring the survivorship curve, the average lifetime, the highest lifetime and the spawning rate of the fruit flies.Results Compared with the model group, Tripterygium wilfordii and liquiritia could reduce the level of trehalose induced by high fat or high sugar, with liquiritia having no significant effect on the triglyceride level in the fruit flies,but enhancing the hypoglycemic and triglyceride effect of Tripterygium wilfordi after Compatibility significantly, which had statistical difference.With respect to regulation of cholesterol levels, Tripterygium ilfordii and liquiritia that played a dominant role in the high fat and high sugar models had synergistic effects when they were combined,which had statistical differences. In addition, the long term administration of Tripterygium wilfordii combining with liquiritia significantly reverses the reduction of the survival rate of fruit flies, the average life span of fruit flies, the maximum life span and the decrease of the amount of spawning caused by Tripterygium wilfordii with statistical differences.Conclusion Tripterygium wilfordii and liquiritia have certain lipid-lowering effects, which can enhance the lipid-lowering activity and reduce the toxicity of Tripterygium wilfordii effectively when they were combined.
引文
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[14] Na J.A Drosophila model of high sugar diet-induced cardiomyopathy[J].PLoS genetics 9,e1003175.
[15] Zhou ZL,Yang YX,Ding J,et al.Triptolide:structural modifications,structure-activity relationships,bioactivities,clinical development and mechanisms[J].Natural product reports 29,457-475.
[2] Lv QW.Comparison of Tripterygium wilfordii Hook F with methotrexate in the treatment of active rheumatoid arthritis (TRIFRA):a randomised,controlled clinical trial[J].Annals of the rheumatic diseases 74,1078-1086.
[3] Tao X,Fan F,Hoffmann V,et al.Therapeutic impact of the ethyl acetate extract of Tripterygium wilfordii Hook F on nephritis in NZB/W F1 mice[J].Arthritis research & therapy 8,R24.
[4] Tao X.Effective therapy for nephritis in (NZB x NZW)F1 mice with triptolide and tripdiolide,the principal active components of the Chinese herbal remedy Tripterygium wilfordii Hook F[J].Arthritis and rheumatism 58,1774-1783.
[5] Manzo SG.Natural product triptolide mediates cancer cell death by triggering CDK7-dependent degradation of RNA polymerase II[J].Cancer research 72,5363-5373.
[6] Wang J.Triptolide inhibits amyloid-beta production and protects neural cells by inhibiting CXCR2 activity[J].Journal of Alzheimer's disease:JAD 33,217-229.
[7] Liu J,Lee J,Salazar Hernandez,et al.Treatment of obesity with celastrol[J].Cell 161,999-1011.
[8] Reis T.Effects of Synthetic Diets Enriched in Specific Nutrients on Drosophila Development,Body Fat,and Lifespan[J].PloS one 11,e0146758.
[9] Dew-Budd K,Jarnigan J.& Reed LK.Genetic and Sex-Specific Transgenerational Effects of a High Fat Diet in Drosophila melanogaster[J].PloS one 11,e0160857.
[10] Baker KD.& Thummel CS.Diabetic larvae and obese flies-emerging studies of metabolism in Drosophila[J].Cell metabolism 6,257-266.
[11] Pasco MY.& Leopold P.High sugar-induced insulin resistance in Drosophila relies on the lipocalin Neural Lazarillo[J].PloS one 7,e36583.
[12] Musselman LP.A high-sugar diet produces obesity and insulin resistance in wild-type Drosophila[J].Disease models & mechanisms 4,842-849.
[13] Birse RT.High-fat-diet-induced obesity and heart dysfunction are regulated by the TOR pathway in Drosophila[J].Cell metabolism 12,533-544.
[14] Na J.A Drosophila model of high sugar diet-induced cardiomyopathy[J].PLoS genetics 9,e1003175.
[15] Zhou ZL,Yang YX,Ding J,et al.Triptolide:structural modifications,structure-activity relationships,bioactivities,clinical development and mechanisms[J].Natural product reports 29,457-475.
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