Department of Clinical Biochemistry, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Department of Clinical Biochemistry, School of Medicine, Yasuj University of Medical Sciences, Yasuj, Iran.
Life Sci. 2019 Sep 15;233:116706. doi: 10.1016/j.lfs.2019.116706. Epub 2019 Jul 29.
Osteoporosis is a common extra-hepatic complication in patients with chronic liver disease. Tumor necrosis factor related apoptosis-inducing ligand (TRAIL), sex hormones, adiponectin, and sclerostin are involved in the regulation of bone turnover but little is known about their role in the promotion of hepatic osteodystrophy. Endogenous opioids are reported to increase during cholestasis and may influence bone resorption. The purpose of this study was to investigate the circulating levels of these factors and their expression in the femur of bile duct ligated (BDL) rats, to evaluate the biomechanical bone strength, and the effect of naltrexone (NTX).
BDL and sham-operated (SO) rats received 10 mg/kg NTX as an opioid-receptors antagonist or saline once daily for 28 days intraperitoneally. Three-point bending test was performed on the right femurs and, plasma bone alkaline phosphatase (BALP), sex hormones, TRAIL, adiponectin, sclerostin, as well as the mRNA expression levels of the latter three proteins, were measured in the femur tissues.
Plasma TRAIL, estrogen, adiponectin, sclerostin and, BALP levels increased in BDL animals when compared to the related controls, whereas testosterone level decreased and NTX reversed these effects significantly. Femur strength decreased in cirrhotic animals and interestingly, blocking opioid-receptors by NTX improved it significantly (p ≤ 0.05).
High levels of TRAIL, adiponectin and, sclerostin after bile duct ligation, suggest that these factors may have some roles in bone loss after cirrhosis. Administration of NTX improved all the mentioned factors except for bone strength. Effect of NTX on bone loss in BDL rats needs more study to clarify.
骨质疏松症是慢性肝病患者常见的肝外并发症。肿瘤坏死因子相关凋亡诱导配体（TRAIL）、性激素、脂联素和硬化素参与骨转换的调节，但它们在促进肝性骨营养不良中的作用知之甚少。据报道，内源性阿片类物质在胆汁淤积时增加，可能影响骨吸收。本研究旨在探讨这些因素的循环水平及其在胆管结扎（BDL）大鼠股骨中的表达，评估生物力学骨强度，并研究纳曲酮（NTX）的作用。
BDL 和假手术（SO）大鼠每天腹膜内给予 10mg/kg NTX 作为阿片受体拮抗剂或生理盐水，共 28 天。对右侧股骨进行三点弯曲试验，测量股骨组织中的血浆骨碱性磷酸酶（BALP）、性激素、TRAIL、脂联素、硬化素以及后三种蛋白的 mRNA 表达水平。
与相关对照组相比，BDL 动物的血浆 TRAIL、雌激素、脂联素、硬化素和 BALP 水平升高，而睾酮水平降低，NTX 则显著逆转了这些效应。肝硬化动物的股骨强度降低，有趣的是，NTX 阻断阿片受体显著改善了这种情况（p≤0.05）。
BDL 后 TRAIL、脂联素和硬化素水平升高，提示这些因素可能在肝硬化后骨丢失中起作用。NTX 的给药改善了除骨强度以外的所有上述因素。需要进一步研究 NTX 对 BDL 大鼠骨丢失的作用，以阐明其作用机制。
