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番石榴叶总三萜对糖尿病肾病大鼠肾损伤的改善作用及机制研究

Effect and mechanism of total triterpenoids from Psidiumguajava leaves on renal injury in rats with diabetic nephropathy

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【作者】 饶姣雨魏崧丞王小康叶开和叶春玲张晓琦吕艳青

【Author】 RAO Jiao-yu;WEI Song-cheng;WANG Xiao-kang;YE Kai-he;YE Chun-ling;ZHANG Xiao-qi;Lü Yan-qing;Department of Pharmacology, College of Pharmacy,Jinan University;Institute of Traditional Chinese Medicine and Natural Medicine, College of Pharmacy,Jinan University;

【通讯作者】 吕艳青;

【机构】 暨南大学药学院药理学教研室暨南大学药学院中药及天然药物研究所

【摘要】 目的探讨番石榴叶总三萜(TTPGL)对糖尿病肾病(DN)大鼠肾功能的保护作用及可能机制。方法用高糖高脂饮食加腹腔注射链脲佐菌素(STZ,35mg·kg-1)建立DN大鼠模型。将造模成功的DN大鼠随机分为5组:模型组、对照组和低、中、高3个剂量实验组;另取正常大鼠作为正常组。模型组和正常组灌胃等剂量0. 9%Na Cl;对照组给予3 mg·kg-1·d-1罗格列酮;低、中、高3个剂量实验组分别给予30,60,120 mg·kg-1·d-1 TTPGL,持续给药8周。用血糖仪测空腹血糖值(FBG);用GPO-PAP法测定总胆固醇(TC);用放射免疫法测定24 h尿蛋白;用逆转录聚合酶链反应检测白细胞介素-6(IL-6)的基因表达水平;用免疫印迹法检测核因子-κB-P65磷酸化的蛋白表达水平。结果中、高2个剂量实验组、对照组和模型组FBG分别为(18. 10±0. 22),(16. 98±0. 20),(15. 53±0. 50)和(22. 23±0. 36) mmol·L-1;上述这4组的TC分别为(3. 20±0. 29),(3. 02±0. 31),(2. 47±0. 48)和(6. 32±0. 60)mmol·L-1;上述这4组的24 h尿蛋白定量分别为(21. 61±1. 60),(20. 42±0. 95),(14. 40±3. 13)和(39. 40±1. 73) mg/24 h;上述这4组的IL-6mRNA表达分别为2. 59±0. 13,1. 50±0. 14,1. 04±0. 10和5. 51±0. 28;上述这4组的核因子-κB-p65磷酸化蛋白相对表达水平分别为4. 04±0. 22,3. 18±0. 14,1. 17±0. 18和6. 14±0. 11;中、高2个剂量实验组和对照组的上述指标与模型组比较,差异均有统计学意义(均P <0. 01)。结论 TTPGL能明显地降低DN大鼠的血糖和血脂水平,改善DN大鼠的肾功能,其机制可能与抑制核因子-κB通路磷酸化水平和IL-6 mRNA的表达有关。

【Abstract】 Objective To investigate the nephro-protective effect of total triterpenoids from Psidiumguajava leaves( TTPGL) on renal injury rats and its possible mechanisms. Methods Diabetic nephropathy( DN) rats were induced by intraperitoneal injection of streptozotocin( STZ,35 mg·kg-1) and a high-fat diet. All the model rats were then divided into 5 groups: model group,control group,and low,medium and high dosage experimental groups,and normal rats were taken as normal group.The model and normal group were intragastrically administered with the same amount of normal saline; control group was given 3 mg·kg-1·d-1 rosiglitazone; low,medium,and high doses of experimental group were given 30,60,120 mg ·kg-1·d-1 TTPGL,continued administration for 8 weeks. Fasting blood glucose( FBG) was detected by blood glucose monitor. Total cholesterol( TC) was detected by GPO-PAP. The 24 h urine protein was determined by radioimmunoassay. The interleukin-6( IL-6) mRNA expression were detected by reverse transcription polymerase chain reaction. The nuclear factor-κB-P65( NF-κB-p65) phosphorylated protein expression was detected by western blotting. Results FBG level in experimental-M and experimental-H groups,control group and model group were( 18. 10 ± 0. 22),( 16. 98 ± 0. 20),( 15. 53 ± 0. 50) and( 22. 23 ± 0. 36) mmol·L-1; TC level in the above 4 groups( 3. 20 ± 0. 29),( 3. 02 ± 0. 31),( 2. 47 ± 0. 48) and( 6. 32 ± 0. 60) mmol · L-1; the 24 h urine protein in the above 4 groups were respectively( 21. 61 ± 1. 60),( 20. 42 ± 0. 95),( 14. 40 ± 3. 13) and( 39. 40 ± 1. 73) mg/24 h; the expression of IL-6 mRNA in the above 4 groups was 2. 59 ± 0. 13,1. 50 ± 0. 14,1. 04 ± 0. 10 and 5. 51 ± 0. 28; the relative expression levels of NF-κB-p65 phosphorylated protein in the above 4 groups were 4. 04 ± 0. 22,3. 18 ± 0. 14,1. 17 ± 0. 18 and6. 14 ± 0. 11,respectively. Comparing between experimental-M,experimental-H and control groups with model group,the differences of the factors were significant( all P < 0. 01). Conclusion TTPGL ameliorated the renal damagein rats with DN by significantly decreasing the glucose and lipid levels. The mechanism may be related to the inhibition of phosphorylation level of NF-kappa B pathway and the expression of IL-6 mRNA.

【基金】 广东省高等学校科技创新重点基金资助项目(cxzd1111);广东省重大科技专项基金资助项目(2013A022100028)
  • 【文献出处】 中国临床药理学杂志 ,The Chinese Journal of Clinical Pharmacology , 编辑部邮箱 ,2019年15期
  • 【分类号】R285.5
  • 【被引频次】9
  • 【下载频次】287
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