重組人甲狀旁腺素1-34對去卵巢大鼠骨質疏松的作用研究

陳波 李翠瓊 朱常青 李婉媚 曹小禎

[摘要] 目的 探討重組人甲狀旁腺素1-34（hPTH1-34）對去卵巢大鼠骨質疏松的治療作用。 方法50只7個月齡SD健康雌性大鼠，30只行雙側卵巢摘除術，20只做假手術（SHAM），12周后各處死10只證實骨質疏松造模成功。余20只雙側卵巢摘除大鼠隨機分為去卵巢（OVX）安慰劑組10只和hPTH1-34治療組10只，10只SHAM組作對照。hPTH1-34治療組劑量為20 μg/kg，皮下注射，每周注射3次。OVX安慰劑和SHAM組皮下注射0.5 mL生理鹽水，每周注射3次。治療3個月后，測定并比較三組股骨、腰椎骨密度（BMD）、血清鈣、磷、骨源性堿性磷酸酶（BALP）、抗酒石酸酸性磷酸酶-5b（Trap-5b）水平。 結果 hPTH1-34治療組股骨和腰椎BMD較OVX安慰劑組明顯升高[（0.151±0.008）g/cm2比（0.135±0.013）g/cm2，（0.181±0.010）g/cm2比（0.159±0.008）g/cm2，P < 0.01]，血清鈣、磷、BALP、Trap-5b水平明顯高于OVX安慰劑組（P < 0.05或P < 0.01），與SHAM組比較差異無統計學意義（P > 0.05）。 結論 hPTH1-34通過刺激成骨細胞的活性，抑制破骨細胞，可顯著增加BMD，對去卵巢大鼠骨質疏松有效。

[關鍵詞] 重組人甲狀旁腺素1-34；骨質疏松癥；骨密度；骨轉換指標

[中圖分類號] R580[文獻標識碼] A[文章編號] 1673-7210（2014）06（b）-0017-04

Effect of human parathyroid hormone (hPTHl-34) on osteoporosis of ovariectomized rats

CHEN Bo1 LI Cuiqiong1 ZHU Changqing1 LI Wanmei1 CAO Xiaozhen2

1.Department of Endocrinology, the 12th People′s Hospital of Guangzhou City, Guangdong Province, Guangzhou 510620, China; 2.Department of Ultrasonography, the 12th People′s Hospital of Guangzhou City, Guangdong Province, Guangzhou 510620, China

[Abstract] Objective To investigate the effects of human parathyroid hormone (hPTHl-34) on the osteoporosis of ovariectomized rats. Methods 50 female 7-month-old SD rats were used for this experiment and 30 of them were ovariectomized and another 20 received sham operation. After 12 weeks of ovariectomy the osteoporosis model was confirmed by use of 10 ovariectomized and sham-operated rats. The osteoporotic rats of 20 were randomly divided into 2 treatment groups: hPTHl-34 and OVX placebo groups with 10 rats in each group, the other 10 rats were sham-operated as the control for SHAM group. Totally hPTHl-34 (20 μg/kg) were subcutaneous injected into the rats of hPTHl-34 group once every other day. The rats of the OVX placebo group and SHAM group were injected with 0.5 mL saline once every other day. The bone mineral density (BMD), serurn Ca, P, bone alkaline phosphatase (BALP), serum tartrate-resistant acid phosphatase 5b (Trap-5b) were measured after 3 months therapy. Results After 12 weeks′treatment the femoral and lumbar BMD in the hPTHl-34 group increased obviously compared with those of OVX placebo group [(0.151±0.008) g/cm2 vs (0.135±0.013) g/cm2, (0.181±0.010) g/cm2 vs (0.159±0.008) g/cm2, P < 0.01]. After treated with hPTHl-34 serum Ca, P, BALP and Trap-5b significantly increased compared with those of OVX placebo group (P < 0.05 or P < 0.01). There was no significant difference in hPTHl-34 and SHAM groups. Conclusion hPTHl-34 can stimulate osteoblast activity, inhibite bone resorption, promote bone mass effect and is effective on protection against osteoporosis.

[Key words] Human parathyroid hormone; Osteoporosis; Bone mineral density; Bone turnover markers

骨質疏松癥（osteoporosis，OP）是一種全身性骨病，以骨量減少和骨的微結構破壞為特征，使骨的脆性增加，并易發生骨折[1]，嚴重影響患者的生活質量。而長期臥床又可加重骨質疏松，并引發其他心肺疾患以致形成惡性循環，甚至造成死亡，給患者、家庭和社會都帶來了沉重的社會及經濟負擔。隨著老齡化社會的到來，骨質疏松癥發病率逐年增長，據統計2005年美國有近250萬人次因骨質疏松性骨折就診，有43.2萬患者因此入院，約18萬患者需要家庭護理[2]，目前全球約有2億患者，中國約9千萬患者[3]，已經成為全球所面臨的重要健康問題。通常臨床上以骨密度（BMD）作為診斷和評價藥物療效的指標，由于BMD是通過測量骨質量反應骨質疏松的情況，作為療效評價指標存在一定的滯后性，不能對患者治療中骨代謝情況進行有效監測。……