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[甲状旁腺激素基因治疗甲状旁腺功能减退症的pcDNA3.1载体:一项实验研究]

[pcDNA3.1 parathyroid hormone gene therapy of hypoparathyroidism: an experimental study].

作者信息

Zhang Weihui, Song Chun, Wen Jimin, Song Chunfang

机构信息

Department of General Surgery, First Affiliated Hospital of Harbin Medical University, Harbin 150001, China.

出版信息

Zhonghua Yi Xue Za Zhi. 2002 Aug 25;82(16):1133-5.

Abstract

OBJECTIVE

To investigate the effect of pcDNA3.1 parathyroid hormone (PTH) gene therapy for hypoparathyroidism and the best dosage.

METHODS

The parathyroid glands of 40 rabbits were resected so as to establish an animal model of hypoparathyroidism. The rabbits were randomly divided into 5 groups of 8 animals. Different doses of pcDNA3.1.PTH (50 micro g/kg, 150 micro g/kg, and 250 micro g/kg) containing human PTH gene, normal saline, and the vacant vector pcDNA3.1 were injected into the muscle of different groups of rabbits: Before parathyroidectomy and 1, 2, 3, 5, 7, 10, 15, 30, and 60 days after the operation blood was drawn to detect the concentrations of calcium and PTH.

RESULTS

The serum calcium and PTH began to increase one day after the injection of pcDNA3.1.PTH, and reached the peak concentrations at the seventh day. The levels lasted for two months. Seven days after the serum calcium and PTH were 2.83 +/- 0.02 mmol/L and 11.303 +/- 0.025 pg/ml respectively in 150 micro g/kg group and were 2.81 +/- 0.07 mmol/L and 12.001 +/- 0.008 pg/ml respectively in 250 micro g/kg group.

CONCLUSION

Human PTH gene therapy is effective in treating HPT with the most effective dose of 150 micro g/kg and 250 micro g/kg.

摘要

目的

探讨pcDNA3.1甲状旁腺激素(PTH)基因治疗甲状旁腺功能减退症的效果及最佳剂量。

方法

切除40只家兔的甲状旁腺以建立甲状旁腺功能减退症动物模型。将家兔随机分为5组,每组8只。分别向不同组家兔肌肉注射不同剂量含人PTH基因的pcDNA3.1.PTH(50μg/kg、150μg/kg和250μg/kg)、生理盐水及空载体pcDNA3.1:在甲状旁腺切除术前及术后1、2、3、5、7、10、15、30和60天采血检测血钙和PTH浓度。

结果

注射pcDNA3.1.PTH后1天血清钙和PTH开始升高,第7天达到峰值浓度。该水平持续两个月。第7天时,150μg/kg组血清钙和PTH分别为2.83±0.02mmol/L和11.303±0.025pg/ml,250μg/kg组分别为2.81±0.07mmol/L和12.001±0.008pg/ml。

结论

人PTH基因治疗甲状旁腺功能减退症有效,最有效剂量为150μg/kg和250μg/kg。

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