温肾固疏方干预绝经后骨质疏松药理研究
Pharmacological research on the effect and mechanism of WenShenGuShu formula in postmenopausal osteoporosis
  
DOI:10.3969/j.issn.1006.7108.2018.04.017
中文关键词:  绝经后骨质疏松  脂代谢  骨代谢  载脂蛋白E
英文关键词:Postmenopausal osteoporosis  Lipid metabolism  Bone metabolism  Apolipoprotein E
基金项目:江苏省研究生科研创新计划项目(KYZZ15-0272)
作者单位
沈蕴茹 郭海英* 南京中医药大学第二临床医学院江苏 南京210023 
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中文摘要:
      目的 观察温肾固疏方对骨代谢造成的影响。方法 将40只大鼠随机分为假手术组、模型组、雌激素组、温肾固疏方高、中、低剂量组。假手术组仅切除卵巢周围脂肪组织,不切除卵巢,其余大鼠切除双侧卵巢,建立绝经后骨质疏松模型。造模1 m后,中药汤剂灌胃干预8 w,末次给药结束后放血处死。双能X射线法测定去势大鼠离体股骨、腰椎骨密度(bone mineral density ,BMD)、骨矿含量(bone mineral content , BMC),电子式双柱万能材料试验机测定股骨弾性模型、最大承载力、刚性、最大应力,全自动生物仪测HDL-C、LDL-C、TG、TC,计算动脉粥样硬化指数(atherogen icindex, AI),采用酶联免疫吸附测定(Elisa)法测量大鼠血清OT/BGP、Lipid、ApoE、sRANKL、OPG、BMPs。结果:与假手术组对比,模型组BMD、BMC下降(P<0.05); 股骨弾性模型、最大承载力、刚性、最大应力皆下(P<0.05);OPG、BMPs下降(P<0.05);Lip上升(P<0.05);ApoE上升(P<0.01);LDL-C上升(P<0.05)。与模型组对比,雌激素、低、高剂量组大鼠股骨BMD、BMC上升(P<0.05);雌激素组、中剂量组弾性模型增高(P<0.05);雌激素组、高剂量组最大承载力增高(P<0.05);低、高剂量组刚性增高(P<0.05);雌激素组、低、高剂量组最大应力增高(P<0.05);雌激素组、低、高剂量组血清OT/BGP上升(P<0.05);低、高剂量组sRANKL下降(P<0.05);雌激素组、低剂量组血清OPG上升(P<0.05);雌激素组、低、高剂量组BMPs上升(P<0.05);高、中、低剂量组血清Lip下降(P<0.05);低剂量组ApoE下降(P<0.05);低、高剂量组LDL-C下降;低剂量组TG下降(P<0.05);低、高剂量组动脉粥样硬化指数下降(P<0.05)。结论:去势大鼠骨质疏松模型的脂代谢是重要调节点,温肾固疏方可以通过调控ApoE水平影响血清脂代谢与骨代谢,对绝经后骨质疏松有一定防治效果,不同剂量的温肾固疏方汤剂对绝经后骨质疏松症的防治效果不同,高剂量组较为明显。
英文摘要:
      Objective The objective of this study is to examine the effect of WenShenGuShu formula on bone metabolism of ovariectomized Rats. Methods Firstly the ovariectomized (OVX) model of SD rats was established, and after 1 month of successful modeling, 40 modeling rats were randomly divided into different groups: WenShenGuShu formula groups with different doses, model group, estradiol valerate group, and sham group with resection of adipose tissue. Then decoction of Chinese medicine was taken orally for 8 weeks, and the blood was sacrificed after the last administration. In this experiment, dual energy x-ray absorptiometry method was used to determine the in vitro BMD and BMC of femur and lumbar vertebra of castrated rats, and femoral biomechanics were measured by electronic double column universal material test. Atherosclerosis index was calculated using automatic biological measurements of HDL-C, LDL-C, TG and TC, and the rat serum OT/BGP, lipid, ApoE, sRANKL, OPG, and BMPs were measured by ELISA. Results The experimental results were as follows: compared with the sham group, in the model group BMD and BMC decreased (P<0.05), and the femoral elastic model, maximum bearing capacity, rigidity and the maximum stress all decreased (P<0.05). The levels of OPG and BMPs also decreased (P<0.05), but the levels of Lip (P<0.05), ApoE (P<0.05) and LDL-C (P<0.01) all increased. Compared with the model group, femoral BMD and BMC of the estrogen and low and high dose groups all increased (P<0.05). The elastic model of the estrogen group and the medium dose group increased (P<0.05), the maximum capacity of the estrogen group and high dose group increased (P<0.05), rigidity of low and high dose groups increased (P<0.05), and the maximum stress of the estrogen group and low and high dose groups increased (P<0.05). Serum OT/BGP of estrogen group and low and high dose groups increased (P<0.05), sRANKL of low and high dose groups decreased (P<0.05), OPG of estrogen group and low dose group increased (P<0.05), and BMPs of estrogen group and low and high dose groups increased (P<0.05). The serum Lip of high, medium and low dose groups decreased (P<0.05). ApoE of low dose group decreased (P<0.05), LDL-C of low and high dose groups decreased, TG of low dose group decreased (P<0.05), and the atherosclerosis index of the low and high dose groups decreased (P<0.05). Conclusions Through the analysis of these experimental parameters, the important conclusion could be reached that lipid metabolism in ovariectomized rat model of osteoporosis is an important regulator. WenShenGuShu formula has certain effect on the prevention of postmenopausal osteoporosis through influencing serum lipid metabolism and bone metabolism by regulating ApoE level. Different doses of WenShenGuShu formula have different control effects on postmenopausal osteoporosis and the effect was greater in the high dose group.
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