黑玉米多糖对糖尿病性骨质疏松大鼠的改善作用及机制研究

曾诚; 刘诗芸; 徐颍; 韩博皓; 杨慧文

doi:10.13386/j.issn1002-0306.2025020180

黑玉米多糖对糖尿病性骨质疏松大鼠的改善作用及机制研究

Study on the Therapeutic Effect and Mechanism of Black Corn Polysaccharide on Diabetic Osteoporosis Rats

摘要

摘要: 目的：探讨黑玉米多糖（Black corn polysaccharide，BPS）对糖尿病性骨质疏松（Diabetic osteoporosis, DOP）大鼠的治疗作用及其机制。方法：采用高脂饮食联合链脲佐菌素构建DOP大鼠模型，随机分为模型组、BPS低剂量组和BPS高剂量组、二甲双胍组，另设对照组。使用血糖仪测定大鼠空腹血糖（Fasting blood-glucose，FBG）、饮食饮水量、体重。采集血清、股骨、胫骨样本；ELISA法测定血清大鼠糖化血红蛋白（Glycosylated hemoglobin，GHb）、大鼠1,25二羟基维生素D3（1,25-(OH)₂D₃）、大鼠甲状旁腺激素（Parathyroid hormone，PTH）、大鼠Ⅰ型前胶原氨基端原肽（N-terminal propeptide of type Ⅰ procollagen，PINP）、大鼠抗酒石酸酸性磷酸酶5b（Tartrate-resistant acid phosphatase 5b，TRACP-5b）、大鼠Ⅰ型胶原交联羧基端肽（Type Ⅰ collagen cross-links the carboxy-terminal peptide，CTX-Ⅰ）、大鼠骨保护素（Osteoprotegerin，OPG）和大鼠核因子κB受体活化因子配体（Receptor activator of nuclear factor-κB ligand，RANKL）含量。通过HE染色观察进行皮质骨和松质骨的骨形态计量学测量。三点弯曲实验测股骨生物力学参数。免疫组化法观察胫骨中OPG、RANKL蛋白表达水平。结果：BPS可降低DOP大鼠的GHb（P<0.01）、FBG（P<0.01），下调血清中TRACP-5b（P<0.01）、CTX-I（P<0.01）水平并上调PTH（P<0.05）、1,25-（OH）₂D₃（P<0.01）、PINP、OPG、OPG/RANKL（P<0.05或P<0.01）水平。此外，BPS可上调大鼠胫骨上段静态参数骨小梁面积百分数（Trabecular area，%Tb.Ar）、骨小梁数量（Number of trabeculae，Tb.N）、皮质骨面积（Cortical bone area，Ct.Ar）和骨髓腔面积百分数（Area of bone marrow cavity，%Ma.Ar）值并减少骨小梁分离度（Trabecular bone dissociation，Tb.Sp）值。同时，BPS可增加大鼠股骨的最大载荷（P<0.01）、最大能量吸收（P<0.01），骨结构的韧性（P<0.01）和股骨的弹性模量（P<0.01）。另外，BPS会增强大鼠骨组织中OPG的表达，并抑制RANKL的表达。结论：BPS可有效降低血糖，改善骨代谢紊乱，提高骨强度，从而发挥抗DOP的作用，其机制可能与OPG/RANK/RANKL信号有关，为DOP的药物研发提供一定的理论依据。

Abstract: Objective: To investigate the therapeutic effect of black corn polysaccharide (BPS) on diabetic osteoporosis (DOP) in rats and explore its underlying mechanisms. Methods: A DOP rat model was established by high-fat diet feeding combined with streptozotocin (STZ) injection. The rats were randomly divided into model group, low-dose BPS group, high-dose BPS group, metformin group, and blank control group. Metabolic parameters including fasting blood glucose (FBG), food and water intake, and body weight were monitored. Serum, femur, and tibia samples were collected. Serum levels of glycosylated hemoglobin (GHb), 1,25-(OH)₂D₃, parathyroid hormone (PTH), N-terminal propeptide of type I procollagen (PINP), tartrate-resistant acid phosphatase 5b (TRACP-5b), C-terminal telopeptide of type I collagen (CTX-I), osteoprotegerin (OPG), and receptor activator of nuclear factor-κB ligand (RANKL) were measured by ELISA. Bone morphometry measurements of cortical bone and cancellous bone were performed by HE staining observation.. Femoral biomechanical properties were assessed using three-point bending test. The protein expressions of OPG and RANKL in tibia were detected by immunohistochemistry. Results: BPS treatment significantly reduced serum levels of GHb (P<0.01) and FBG (P<0.01), decreased bone resorption markers TRACP-5b (P<0.01) and CTX-I (P<0.01), while increased PTH (P<0.05), 1,25-(OH)2D3 (P<0.01), PINP, OPG levels and OPG/RANKL ratio (P<0.05 or P<0.01). BPS improved tibial bone microstructure by increasing trabecular area percentage (%Tb.Ar), trabecular number (Tb.N), cortical bone area (Ct.Ar) and bone marrow cavity area percentage (%Ma.Ar), while decreasing trabecular separation (Tb.Sp). Moreover, BPS enhanced femoral biomechanical properties including maximum load (P<0.01), maximum energy absorption (P<0.01), structural toughness (P<0.01) and elastic modulus (P<0.01). In addition, BPS upregulated OPG expression and downregulated RANKL expression in bone tissue. Conclusion: BPS effectively improves glycemic control, ameliorates bone metabolic disorders and enhances bone strength in DOP rats, possibly through regulating the OPG/RANK/RANKL signaling pathway. These findings provide a theoretical basis for developing BPS as a potential therapeutic agent for diabetic osteoporosis.

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