补肾阳方拮抗外源性糖皮质激素下丘脑-垂体-肾上腺轴抑制及分解代谢效应的研究  

Effects of kidney-yang tonic formula on inhibition of HPA axis and catabolism by glucocorticoids

作　　者：曾洋 段晓红[2] 孙伟 马方励 黄建华[2] 

机构地区：[1]上海市杨浦区安图医院肾病科,200093 [2]复旦大学附属华山医院中西医结合研究所 [3]无限极(中国)有限公司

出　　处：《中华临床医师杂志（电子版）》2012年第23期7556-7560,共5页Chinese Journal of Clinicians(Electronic Edition)

基　　金：国家自然科学基金(30901888)

摘　　要：目的本研究观察了补肾阳方拮抗外源性糖皮质激素下丘脑-垂体-肾上腺(HPA)轴抑制及分解代谢的效果及机制。方法 SD大鼠分为对照组、模型组、模型+补肾阳复方低、中、高剂量组。采用皮质酮注射造成肾阳虚模型。第7天、第14天称动物体重。第14天称肾上腺重量,计算肾上腺重量指数(肾上腺/体重)。采用ELISA法检测血浆促肾上腺皮质激素(ACTH)、皮质酮浓度;取肾上腺,进行全基因组表达谱芯片检测及分析。结果糖皮质激素造模导致大鼠体重降低,补肾阳方在第7、14天均能保持体重。补肾阳方治疗使模型组下降的肾上腺重量升高。对照组、模型组、模型+补肾阳复方低、中、高剂量组血浆ACTH水平分别为(324.46±132.92)pg/ml、(150.25±60.54)pg/ml、(315.64±285.51)pg/ml、(330.57±224.046)pg/ml、(305.57±209.57)pg/ml,各治疗组与模型组比较,显著升高(P<0.05)。各组血浆皮质酮水平(16.22±7.65)ng/ml、(5.50±4.05)ng/ml、(7.70±2.67)ng/ml、(8.36±2.84)ng/ml、(7.85±3.59)ng/ml,补肾阳复方中剂量与模型组比较,差异有统计学意义(P<0.05)。基因芯片结果筛选出了模型组上调或下调的基因,而能被补肾阳复方逆转的基因828个,功能分析显示涉及类固醇合成酶和细胞增殖通路。结论补肾阳方保护糖皮质激素肾阳虚证模型的HPA轴功能;能拮抗糖皮质激素分解效应。Objective To investigate effects and mechanisms of kidney-yang tonifying formula on inhibition of HPA axis and catabolism by glucocorticoids.Methods SD rats were devided into control,model,model plus low,middle and high dose of formula group.Model was generated by injection of corticosterone.Body weight was measured in the 7th and 14th day.Adrenal weight was weighed and adrenal index(adrenal weight /body weight) was calculated.The level of plasma adrenocorticotrophin(ACTH),corticosterone was measured by ELISA.Whole-genome microarray analysis was conducted on adrenal gland sample.Results Exogenous glucocorticoids resulted in decrease in body weight gain which was protected by kidney-yang tonic(KYT) formula.The formula also increased the adrenal weight.The plasma level of ACTH in control,model and drug treatment group was(324.46 ± 132.92) pg /ml,(150.25 ± 60.54) pg /ml,(315.64 ± 285.51) pg /ml,(330.57 ± 224.046) pg /ml,(305.57 ± 209.57) pg /ml respectively.Compared to model,KYT significantly increased the level of ACTH(P < 0.05).The plasma level of corticosterone was(16.22 ± 7.65) ng /ml,(5.50 ± 4.05) ng /ml,(7.70 ± 2.67) ng /ml,(8.36 ± 2.84) ng /ml,(7.85 ± 3.59) ng /ml respectively.Compared to model group,the level of corticosterone in middle dose of KYT group significantly increased(P < 0.05).828 genes differentially regulated in model,and reversed by treatment group were captured,which were enriched in steroid biosynthesis and cell proliferation.Conclusions Kidney-yang tonifying drugs protect the inhibited adrenal function,and counteract the catabolic effects of glucocorticoids.

关 键 词：肾阳虚 基因表达 肾上腺皮质 

分 类 号：R285.5[医药卫生—中药学]