探討綠原酸延緩骨質疏鬆之作用及機制-以高血糖高血脂 ApoE-/- 小鼠的動物模式為例

高血脂血糖增加體內活性氧及發炎反應，活化蝕骨細胞導致骨質疏鬆。綠原酸 (Chlorogenic acid, CGA) 具抗氧化、抗發炎的功效，目前 CGA 在骨質疏鬆的作用尚未清楚。本研究旨在探討 CGA 在高血脂血糖中延緩骨質疏鬆的作用及機制。研究方法以 Streptozotocin (STZ) 及高脂飲食 (High fat diet, HFD) (HS 組) 誘導 ApoE-/- 小鼠高血脂血糖，同時給予 CGA，並以抗氧化劑 N -乙醯半胱胺酸 (N-acetylcysteine, NAC) 作為對照。結果顯示 CGA 顯著降低血糖、膽固醇 (Cholesterol , CHO)、三酸甘油脂 (Triglyceride, TG)、低密度脂蛋白 (Low-density lipoprotein , LDL) 及糖化血色素 (Glycosylated Hb, HbA1c) (P<0.05)。組織染色結果顯示 HS 組小鼠股骨的骨小樑減少。Micro CT 結果顯示，CGA 與 HS 相比，骨量 (Bone volume/tissue volume, BV/TV%)、骨小樑厚度 (Trabecular thickness, Tb.Th)、骨小樑數量 (Trabecular number, Tb.N) 及網狀結構連接密度 (Connectivity density, Conn.Dn) 顯著增加 (P<0.05);骨小樑平均寬度 (Trabecular separation, Tb.Sp)、骨小樑表面凹凸程度 (Trabecular pattern factor, Tb.Pf) 及結構模型參數 (Structure model index, SMI) 顯著減少 (P<0.05)。免疫組織染色結果顯示，與 HS 相比，CGA 組小鼠之骨組織白血球介素-6 (Interleukin-6, IL-6)、核因子紅血球2相關因子2 (Nuclear factor erythroid 2-related factor 2, Nrf2)、NF-κB 受體激活蛋白 (Receptor activator of nuclear factor κ B, RANK) 顯著減少，骨橋蛋白 (Osteopontin, OPN) 顯著增加。結果顯示 CGA 具降血糖血脂、抗氧化、抗發炎功效並能有效延緩高血脂血糖引起的骨質疏鬆。

Hyperlipidemia and hyperglycemia increase reactive oxygen species and inflammatory responses to activate osteoclasts then lead to osteoporosis. Chlorogenic acid (CGA) has antioxidant and anti-inflammatory effects. However, the role of CGA in osteoporosis remains unclear. In this study, we explore the effects and mechanisms of chlorogenic acid in mitigating osteoporosis under the circumstance of hyperlipidemia and hyperglycemia. ApoE-/- mice were treated with streptozotocin (STZ) and a high fat diet (HFD) (HS group), alone with chlorogenic acid (CGA); the antioxidant N-acetylcysteine (NAC) was a control to compare the effects. CGA significantly decreased plasma levels of blood glucose, CHO, TG, LDL, and HbA1c (P<0.05). Histological H&E Stain results showed that the mice in HS group reduced the number of trabecular bone in the femurs. The micro CT results showed that as compared to HS group, CGA significantly increased bone volume/tissue volume (BV/TV%), trabecular thickness (Tb.Th), trabecular number (Tb.N), and connectivity density (Conn.Dn) (P<0.05); decreased trabecular separation (Tb.Sp), trabecular pattern factor (Tb.Pf), and structure model index (SMI) (P<0.05), respectively. Histological results of IF Stain showed that compared to HS group, CGA significantly decreased interleukin-6 (IL-6), nuclear factor erythroid 2-related factor 2 (Nrf2) and receptor activator of nuclear factor κ B (RANK); increased osteopontin (OPN). These findings indicate that CGA can reduce hyperlipidemia and hyperglycemia, with antioxidative and anti-inflammatory properties, and can effectively mitigate osteoporosis caused by hyperlipidemia and hyperglycemia.