135459-87-9
135459-87-9 結構式
基本信息
雷奈酸鍶
雷尼酸鍶
5-[雙(羧甲基)氨基]-2-羧基-4-氰基-3-噻吩乙酸二鍶
S 12911
Protelos
S 12911-2
TrontiuMranelate
Srtontiumranelate
StrontiuM Ranelic
STRONTIUM RANELATE
Ranelate StrontiuM
StronitiuM ranelate
物理化學性質
安全數據
常見問題列表
雷尼酸鍶具有抑制骨吸收，促進骨形成的雙重藥理作用。一方面在成骨細胞富集的細胞中，能增大膠原蛋白與非膠原蛋白的合成，通過增強前成骨細胞的增殖而促進成骨細胞介導的骨形成。另一方面，通過降低破骨細胞分化和再吸收活性，減少骨吸收，從而使得骨更新重新達到平衡，有利于骨形成。
雷奈酸鍶主要通過鍶原子，發(fā)揮其藥理作用，鍶是一種與鈣同族的堿土金屬元素，在元素周期表中位于鈣的下方。其吸收、分布、排泄與鈣相似?？诜?g以后。鍶的絕對生物利用度為27％。大劑量的鍶能使骨礦代謝發(fā)生異常，低劑量的鍶能增強前成骨細胞復制，增加成骨細胞的數量，刺激骨形成；同時還能降低破骨細胞的活性，減少破骨細胞的數量，降低骨吸收的速率。在動物和人體內研究也得到的結果相吻合。
骨質疏松癥（OP）是一種進行性骨骼疾病，其特征為骨密度（BMD）降低和骨組織顯微結構發(fā)生退行性改變。表現為骨脆性提高和易發(fā)生骨折，后者以脊椎、髖部和腕處最為常見。婦女由于在停經后或者接受手術切除卵巢后，體內停止產生能保持骨質強硬的雌激素。因此，原發(fā)性OP在停經后或更年期婦女中尤為多見。
目前常用于治療骨質疏松的藥物有兩類：一類為抑制破骨細胞活性從而抑制骨吸收的藥物，如二膦酸鹽、雌激素、降鈣素等；第二類為促進成骨細胞活性從而刺激骨形成的藥物，目前僅有人重組甲狀旁腺素1-34一個產品上市，需要注射給藥，藥價較高。
| Target | Value |
| Calcium channel | 0.5 mM |
Strontium Ranelate (0.1-1 mM; 22 days; Mouse calvaria cells) treatment shows the expression of mRNA for early osteoblast markers (alkaline phosphatase, ALP) is visualized by day 5, while late markers (osteocalcin, OCN) are detectable only by day 15 and beyond.
Strontium Ranelate (0.1-1 mM; 22 days; Mouse calvaria cells) treatment results in significantly increases the mRNA expression of the osteoblastic markers ALP, BSP and OCN at day 22 of MC cell culture.
Strontium Ranelate is found to increase alkaline phosphatase activity and prostaglandin E2 production in a COX-2 dependent manner in murine marrow stromal cells.
RT-PCR
| Cell Line: | Mouse calvaria (MC) cells |
| Concentration: | 0.1 mM, 0.3 mM or 1 mM |
| Incubation Time: | 22 days |
| Result: | The expression of mRNA for early osteoblast markers (ALP) was visualized by day 5, while late markers (OCN) were detectable only by day 15 and beyond. |
Western Blot Analysis
| Cell Line: | Mouse calvaria (MC) cells |
| Concentration: | 0.1 mM, 0.3 mM or 1 mM |
| Incubation Time: | 22 days |
| Result: | Significantly increased the mRNA expression of the osteoblastic markers ALP, BSP and OCN at day 22 of MC cell culture. |
Strontium Ranelate increases bone formation and decreased bone resorption, which results in increased bone mass in the vertebrae of intact adult mice.
In intact adult rats, Strontium Ranelate also increases bone mass, as measured by dual-energy X-ray absorptiometry, in lumbar vertebra and femur, and this is confirmed by histological assessment of trabecular bone volume in the tibial metaphysis.
Strontium Ranelate is found to decrease bone resorption and to increase bone formation in alveolar bone in normal adult monkeys (Macaca fascicularis), which exhibits extensive bone remodeling.
In ovariectomized rats, short-term (3 months) treatment with Strontium Ranelate prevents trabecular bone loss induced by oestrogen deficiency, as demonstrated by bone ash, bone mineral content and histomorphometric analysis in the tibial metaphysis. This effect results from decreased bone resorption while bone formation was maintained. These beneficial effects of Strontium Ranelate on bone mass and microarchitecture in ovariectomized rats are confirmed in long-term experiments. In this long-term study (2 years), the increase in bone mass and microarchitecture induced by Strontium Ranelate results in a marked improvement in bone strength, supporting the beneficial effect of this drug on bone resistance.