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[甲状旁腺功能减退症的pCKM - mPTH重组质粒疗法:大鼠体内实验研究]

[pCKM-mPTH recombinant plasmid therapy for hypoparathyroidism: an in vivo experimental research with rats].

作者信息

Wang Shen-ming, Zhu Yi-fan, Wang Jin-song

机构信息

Department of Thyroid Surgery, First Affiliated Hospital of Sun Yat sen University, Guangzhou 510080, China.

出版信息

Zhonghua Yi Xue Za Zhi. 2004 Dec 17;84(24):2107-9.

PMID:15730628
Abstract

OBJECTIVE

To investigate the effect of gene therapy with pCKM-mPTH recombinant plasmid on hypoparathyroidism.

METHODS

Thirty male Sprague Dawley rats were randomly divided into three groups: group A, undergoing fake operation and then injection of normal saline into the quadriceps muscle of the left leg; group B, undergoing parathyroidectomy and injection of blank pcDNA3.1(+) plasmid into the quadriceps muscle of the left leg; and group C, undergoing parathyroidectomy injection of pCKM-mPTH plasmid containing gene of mutated proparat-hormone into the quadriceps muscle of the left leg. Peripheral blood was collected from each rat before operation and 3, 5, 6, 7, 9, 12, 15, 20 and 30 days after operation. Radioimmunoassay was used to detect the level of parathyroid hormone.

RESULTS

The level of paratheproid hormone (PTH) of the group B was 10.61 ng/dl +/- 0.86 ng/dl before injection of blank plasmid and gradually decreased after the injection, for example, 10.39 ng/dl +/- 0.36 ng/dl 1 day after the injection and 9.45 ng/dl +/- 2.64 ng/dl 60 days after the injection. The level of PTH of the group C was 10.75 ng/dl +/- 0.45 ng/dl before the injection of pCKM-mPTH plasmid and gradually increased after the injection, for example, 28.39 +/- 0.22 ng/dL 1 day after the injection, significantly higher than that before the injection, peaked on the 6th day (43.28 ng/dl +/- 2.45 ng/dl), then gradually decreased, and reached 15.32 ng/dl +/- 0.26 ng/dl on the 60th day. However, the levels of PTH in the group C at any time-point were all significantly higher than those of the group B (all P < 0.01). Symptoms of hypoparathyroidism were not observed in the rats of the group C.

CONCLUSION

pCKM-mPTH recombinant plasmid therapy is effective in treatment of hypoparathyroidism.

摘要

目的

探讨pCKM - mPTH重组质粒基因治疗对甲状旁腺功能减退症的影响。

方法

将30只雄性Sprague Dawley大鼠随机分为三组:A组,行假手术,然后向左侧股四头肌注射生理盐水;B组,行甲状旁腺切除术,然后向左侧股四头肌注射空白pcDNA3.1(+)质粒;C组,行甲状旁腺切除术,然后向左侧股四头肌注射含突变型甲状旁腺激素基因的pCKM - mPTH质粒。于术前及术后3、5、6、7、9、12、15、20和30天采集每只大鼠的外周血。采用放射免疫分析法检测甲状旁腺激素水平。

结果

B组在注射空白质粒前甲状旁腺激素(PTH)水平为10.61 ng/dl±0.86 ng/dl,注射后逐渐下降,如注射后1天为10.39 ng/dl±0.36 ng/dl,注射后60天为9.45 ng/dl±2.64 ng/dl。C组在注射pCKM - mPTH质粒前PTH水平为10.75 ng/dl±0.45 ng/dl,注射后逐渐升高,如注射后第1天为28.39±0.22 ng/dL,显著高于注射前,在第6天达到峰值(43.28 ng/dl±2.45 ng/dl),然后逐渐下降,在第60天降至15.32 ng/dl±0.26 ng/dl。然而,C组在任何时间点的PTH水平均显著高于B组(均P<0.01)。C组大鼠未观察到甲状旁腺功能减退症状。

结论

pCKM - mPTH重组质粒治疗对甲状旁腺功能减退症有效。

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