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胰岛素和甲状旁腺激素在雌性大鼠实验性诱导糖尿病性骨质疏松症治疗中的有益作用:骨矿物质密度、形态计量学和组织学研究。

The beneficial roles of insulin and parathyroid hormones in the treatment of experimentally induced diabetic osteoporosis in female rats: bone mineral density, morphometric and histological studies.

作者信息

Abd El Aziz G S, Ramadan W S, El-Fark M O, Saleh H A M

机构信息

Faculty of medicine king abdulaziz univ, Jeddah, Saudi Arabia.

出版信息

Folia Morphol (Warsz). 2016;75(3):341-354. doi: 10.5603/FM.a2015.0129. Epub 2015 Dec 29.

DOI:10.5603/FM.a2015.0129
PMID:26711653
Abstract

BACKGROUND

Diabetes mellitus (DM) and osteoporosis are two frequent medical conditions with an increasing prevalence in elderly people and are responsible for large number of incurable fractures. This study is designed experimentally in female rats in order to determine whether combined treatment of insulin and parathyroid hormone (PTH) enhances the reversibility of the osteoporotic changes that occurred in streptozotocin (STZ)-induced DM.

MATERIALS AND METHODS

In this study, 30 adult female rats aged 3 months were used, they were randomly divided into: control group (6 rats) and diabetes group (24 rats), in which experimental DM was induced by i.p. injection of a single dose of STZ (60 mg/kg/body weight). Diabetic group was further divided into four subgroups (6 rats each): non-treated diabetic, insulin-treated (8-12 units s.c./day of Humalin U-40), PTH-treated (6.0 μg s.c./kg/day) and combined insulin and PTH-treated subgroups. All tested groups were assessed for body weight, food and water consumptions.

RESULTS

At the end of the experimental period, the bone mineral density (BMD) was measured for all rats of different groups; then the rats were sacrificed and blood samples were collected for measuring glucose, alkaline phosphatase and osteocalcin levels. Right femora were dissected out and subjected to measurement of diameter of neck and shaft, length of shaft, and weight. Then the femora specimens were processed and stained with haematoxylin and eosin for histological study. The results showed that there was a statistically significant, decrease in BMD, increase in the level of alkaline phosphate, and decrease in the level of osteocalcin in rats in diabetic group compared with other groups; these parameters improved in other groups, especially in diabetes/insulin/PTH group. The rats in diabetic group showed statistically significant decrease in neck and shaft diameters and weight of femur bone compared with other groups, while rats in diabetes/insulin/PTH group showed a significant improvement of these parameters. In diabetic group, there were different histopathological changes in cortical bone and Haversian canals, which improved in other groups, especially in rats in diabetes/insulin/PTH group.

CONCLUSIONS

The untreated DM resulted in dramatic reduction in BMD and morphometric parameters. Treatment with insulin ameliorated these effects to some extent, while PTH co--treatment had a more positive effect. The combination of PTH and insulin resulted in stronger improvement of all parameters to approximately like those of control rats.

摘要

背景

糖尿病(DM)和骨质疏松症是老年人中两种常见且患病率不断上升的疾病,它们导致大量无法治愈的骨折。本研究在雌性大鼠中进行实验,以确定胰岛素和甲状旁腺激素(PTH)联合治疗是否能增强链脲佐菌素(STZ)诱导的糖尿病中发生的骨质疏松变化的可逆性。

材料与方法

本研究使用了30只3月龄的成年雌性大鼠,将它们随机分为:对照组(6只大鼠)和糖尿病组(24只大鼠),其中通过腹腔注射单剂量STZ(60 mg/kg体重)诱导实验性糖尿病。糖尿病组进一步分为四个亚组(每组6只大鼠):未治疗的糖尿病组、胰岛素治疗组(优泌林U - 40,皮下注射8 - 12单位/天)、PTH治疗组(皮下注射6.0 μg/kg/天)以及胰岛素和PTH联合治疗亚组。对所有测试组的体重、食物和水消耗量进行评估。

结果

在实验期结束时,测量了不同组所有大鼠的骨矿物质密度(BMD);然后处死大鼠并采集血样以测量血糖、碱性磷酸酶和骨钙素水平。取出右股骨,测量其颈和骨干直径、骨干长度以及重量。然后对股骨标本进行处理并用苏木精和伊红染色以进行组织学研究。结果表明,与其他组相比,糖尿病组大鼠的BMD有统计学意义的降低、碱性磷酸酶水平升高以及骨钙素水平降低;其他组这些参数有所改善,尤其是糖尿病/胰岛素/PTH组。与其他组相比,糖尿病组大鼠的股骨颈和骨干直径以及股骨重量有统计学意义的降低,而糖尿病/胰岛素/PTH组大鼠这些参数有显著改善。在糖尿病组,皮质骨和哈弗斯管存在不同的组织病理学变化,其他组有所改善,尤其是糖尿病/胰岛素/PTH组的大鼠。

结论

未经治疗的糖尿病导致BMD和形态学参数显著降低。胰岛素治疗在一定程度上改善了这些影响,而PTH联合治疗有更积极的效果。PTH和胰岛素联合使用使所有参数有更强的改善,接近对照组大鼠的水平。

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