石斛多糖对SHR氧化应激反应和晚期糖基化终产物代谢的影响

Effects of Dendrobium polysaccharides on oxidative stress and metabolism of advanced glycation end products of SHR

目的 探讨石斛多糖对自发性高血压大鼠(SHR)氧化应激和晚期糖基化终产物(AGE)代谢的药效及其剂量。方法 提取石斛多糖,将SHR大鼠随机分为对照组、低剂量组、中剂量组和高剂量组四个组,对照组给予开水,低剂量组、中剂量组和高剂量组分别给予石斛多糖100mg/d、300mg/d、500mg/d,干预2个月,比较干预后各组超氧化物歧化酶(SOD)、过氧化氢酶(CAT)、丙二醛(MDA)、AGE、可溶性AGE受体(sRAGE)和全长AGE受体(RAGE)mRNA水平。结果 对照组SOD、CAT和MDA平均水平分别为(111.26±23.36)U/L、(59.58±13.48)U/L和(19.77±1.61)μmol/L,低剂量组为(151.18±23.76)U/L、(63.36±12.40)U/L和(10.95±2.07)μmol/L,中剂量组为(177.03±29.00)U/L、(76.35±11.20)U/L和(8.83±1.91)μmol/L,高剂量组为(182.77±21.62)U/L、(85.83±11.58)U/L和(6.94±1.84)μmol/L。与对照组比较,低剂量组SOD水平较高,MDA水平较低,差异有统计学意义(P<0.01),中剂量组和高剂量组SOD、CAT水平较高,MDA水平较低,差异有统计学意义(P<0.01)。对照组AGE、sRAGE和RAGEmRNA平均水平分别为(6.43±0.78)mg/L、(1.09±0.18)mg/L和(0.94±0.11),低剂量组为(6.40±0.80)mg/L、(1.41±0.19)mg/L和(0.90±0.08),中剂量组为(5.99±0.67)mg/L、(1.70±0.20)mg/L和(0.84±0.15),高剂量组为(4.67±0.69)mg/L、(1.95±0.22)mg/L、(0.54±0.10)。与对照组比较,低剂量组、中剂量组sRAGE水平较高,差异有统计学意义(P<0.01),高剂量组AGE、RAGEmRNA水平较低,sRAGE水平较高,差异有统计学意义(P<0.01)。石斛多糖对MDA、SOD、AGE、sRAGE和RAGEmRNA平均水平有剂量效应关系,纠正SHR氧化应激功能紊乱的有效剂量为300mg/d;纠正SHR晚期糖基化终产物及其受体功能紊乱的有效剂量为500mg/d。结论 石斛多糖可有效缓解SHR的氧化应激功能紊乱,降低AGE水平,提高sRAGE水平,降低RAGE基因的活化,对缓解SHR的血管重塑有积极的作用。其药效有剂量效应关系,中等剂量可有效改善氧化应激症状,高剂量能改善AGE其受体症状。

Objective To investigate the effect and dose of Dendrobium polysaccharide on the oxidative stress and metabolism of advanced glycation end products(AGE) in spontaneously hypertensive rats(SHR). Methods Dendrobium polysaccharide was extracted,and SHR were randomly divided into the following four groups: control group,low dose group,middle dose group and high dose group.The control group were given boiled water,while the low dose group,the middle dose group and the high dose group were given 100 mg/d,300 mg/d and 500 mg/d of Dendrobium polysaccharide,respectively.All groups were intervened for 2 months.The levels of superoxide dismutase(SOD),catalase(CAT),malondialdehyde(MDA),AGE,soluble receptor for advanced glycation end products(sRAGE) and receptor for advanced glycation end products(RAGE) mRNA were compared between groups. Results The average levels of SOD,CAT and MDA in the control group were (111.26±23.36) U/L,(59.58±13.48) U/L and (19.77±1.61)μmol/L,respectively.Those in the low dose group were (151.18±23.76) U/L,(63.36±12.40) U/L and (10.95±2.07)μmol/L,respectively.Those in the middle dose group were (177.03±29.00) U/L,(76.35±11.20) U/L and (8.83±1.91)μmol/L,respectively,while those in the high dose group were (182.77±21.62)U/L,(85.83±11.58)U/L and (6.94±1.84)μmol/L,respectively.Compared with the control group,the SOD level in the low dose group was higher and the MDA level was lower,difference was statistically significant( P <0.01),the SOD and CAT levels in the middle dose group and the high dose group were higher and the MDA levels were lower,the difference was statistically significant( P <0.01).The average levels of the AGE,sRAGE and RAGE in the control group were (6.43±0.78) mg/L,(1.09±0.18) mg/L and (0.94±0.11),respectively.Those in the the low dose group were (6.40±0.80) mg/L,(1.41±0.19) mg/L and (0.90±0.08),respectively.Those in the the middle dose group were (5.99 ±0.67) mg/L,(1.70±0.20) mg/L and (0.84±0.15),respectively,while those of the high dose group were (4.67±0.69)mg/L,(1.95±0.22) mg/L,and (0.54±0.10),respectively.Compared with the control group,the sRAGE levels in low dose group and middle dose group were higher,the difference was statistically significant( P <0.01),the AGE and RAGE levels in high dose group were lower,and the sRAGE level was higher,the difference was statisticallysignificant( P <0.01).Dendrobium polysaccharide has dose-effect relationship on the average levels of MDA,SOD,AGE,sRAGE and RAGE mRNA.The effective dose for correcting the oxidative stress disorder of SHR was 300 mg/d,and the effective dose for correcting the dysfunction of AGE and their receptors in SHR was 500 mg/d. Conclusion Dendrobium polysaccharide can effectively alleviate the oxidative stress disorder of SHR,decrease the level of AGE,increase the level of sRAGE,reduce the activation of RAGE gene,and play a positive role in alleviating the vascular remodeling of SHR.The pesticide effect of it has a dose-effect relationship.Medium dose can effectively improve the symptoms of oxidative stress,and high dose can improve the symptoms of AGE receptors.