- 學位論文
利飛亞對卵巢切除大鼠之膝部退化性關節炎的影響
The effects of Tibolone on osteoarthritis in ovariectomized rats
摘要
退化性骨關節炎是一種慢性疾病，其原因眾多。在台灣因嚴重退化性骨關節炎而耗費不眥。退化性膝關節炎通常是由關節區域之軟骨組織發生漸進式病變所致。因為傳統雌激素荷爾蒙療法如口服premarin 0.625毫克有其缺點，因而有新一代的荷爾蒙療法藥物如利飛亞tibolone或是鈣穩raloxifene被研發出來；新一代荷爾蒙療法藥物關於退化性關節炎的研究較少，同時對於退化性關節炎疼痛之改善效果也不清楚。 本研究主要以雌性Wistar大鼠為材料，麻醉後進行一側膝之前十字韌帶切除手術 (對側腳則為控制組) ，其中有三組老鼠再加上卵巢切除手術，術後六週後給予選擇性組織雌激素調節藥物（利飛亞）每兩天一次，治療劑量分別是0.1毫克卅每天以及0.5毫克卅每天，連續十四週。 實驗發現經卵巢切除會加強以前十字韌帶切除後誘發大鼠膝部退化關節炎，因而造成顯著膝部周徑變寬。一旦給予tibolone，老鼠其疼痛行為會改善、膝部周徑腫脹減緩且病理切片結果亦顯示退化關節炎的程度減輕。大鼠血中之鈣、磷以及鹼性磷酸酶各組間不具明顯之差異。組織切片方面，經卵巢切除亦加強前十字韌帶切除後誘發大鼠膝部退化關節炎之發炎細胞浸潤、間質纖維由表皮層入中間區域。給于高劑量tibolone之後，發炎情況改善、間質纖維減少但要給予高劑量較明顯才具統計意義之差異。 本研究之結論為以前十字韌帶切除後誘發大鼠膝部退化關節炎並經卵巢切除誘發更年期之動物模式是可行的，至於荷爾蒙療法tibolone對於使用減緩退化性關節炎亦有成效。希望本研究之結果對於更年期有其明顯症狀又罹患退化性關節炎之婦女在藥物的使用方面能夠提供一些幫助。
並列摘要
Osteoarthritis (OA) is the most common chronic joint disorder in the world and there were many cases. The pathogenesis was the damage of cartilage in the joint region. In some animal studies such as the research from Sneiker’s et al., ovariectomy enhances the severity of collagen induced arthritis in rats. If hormone replacement therapy (HRT) was added, the bone mass increased and inflammation was inhibited. Because there are some disadvantages of traditional HRT drugs like premarin 0.625 mg, new HRT drugs like tibolone or raloxifene were newly developed. The effects of these new drugs on bone were not fully studied. This study uses the model of ovariectomized Wistar rats with OA induced by anterior cruciate ligament transection (ACLT) of one knee. Rats were placed into 6 groups: Group I: control sham operation, Group II: ovariectomized group, Group III: ACLT group, Group IIII: ACLT+ ovariectomized Group, V: ACLT+ ovariectomized+ Tibolone low dose(0.1 mg/day), Group VI: ACLT + ovariectomized + Tibolone high dose(0.5 mg/day). These drugs were given every 2 days after operation 6 weeks, persisting 14 weeks. Gross morphology, pain behaviors changed due to OA of knee joints progressing and histopatholgy (Mankin grading) of the femoral condyles were assessed. Besides, Ca, P and alkaline phophatase levels in the serum were also measured. We found severe knee joint swelling and most obvious pain behaviors occurred in rats of ovariectomized +ACLT group. After of high doses of tibolone was given, knee swelling and pain behaviors improved. Ca, P and alkaline phosphatase level in the serum showed no significant difference between 6 groups. In histopathology, ovariectomy enhanced most obvious inflammatory infiltration into synovium replacing cartilage and fibroplasias in arthritic rats. After high dose of tibolone using, inflammatory infiltrate improved and only focal fibroplasias was noted. In conclusion, this OA induced by ACLT with ovariectomy animal model is feasible and can provide a valuable contribution to the development of new guide about HRT on OA patients. Tibolone do have good effects to improve OA. This result may appear some beneficial to choose drug for those postmenopausal women with OA.
參考文獻
延伸閱讀
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