Department of Nephrology, Zhongshan Hospital of Traditional Chinese Medicine, Zhongshan, 528400, China.
Cardiovascular and Cerebrovascular Drugs Research and Development Center, Tianjin Institute of Medical and Pharmaceutical Sciences, Tianjin, 300020, China.
J Ethnopharmacol. 2021 Jul 15;275:114126. doi: 10.1016/j.jep.2021.114126. Epub 2021 Apr 17.
Triangle grass is a liliaceous Chlorophytum perennial herb of ChlorophytumlaxumR.Br. It is distributed mainly in Guangdong and Guangxi Provinces of China. The initial use of triangle grass was mainly to treat bone pain and swelling caused by a fall injury. Triangle grass tablets (NO. Z20070544) are also used as a preparation in our hospital because of their analgesic, anti-inflammatory, anti-snake venom and microcirculation improvement properties and other pharmacological effects (Mei et al., 2006). Triangle grass tablets have been widely used in our hospital to treat patients with bone pain from chronic kidney disease-mineral and bone disorder (CKD-MBD). However, the effects and mechanism of triangle grass on bone metabolism in chronic kidney disease complicated with mineral and bone abnormalities are unclear.
The aim of the present study was to investigate the effects of a triangle grass decoction on bone metabolism in CKD-MBD rats.
CKD-MBD model rats were subjected to 5/6 nephrectomy combined with 0.5 g NaHPO/rat. Serum blood urea nitrogen (BUN), creatinine (Cr), phosphorus (P), calcium (Ca), and intact parathyroid hormone (iPTH) levels were measured with an automatic biochemical analyser. Bone mineral density was determined with a Viva CT 40 system. Bone morphogenetic protein 7(BMP-7),runt-related transcription factor 2 (Runx2) and Osterix protein levels were measured by Western blot analysis. Kidney, vertebra and thoracic aorta tissue samples were assessed by histopathology and immunohistochemistry (IHC).
The degrees of membrane thickening, necrosis, swelling and cast deposition were significantly reduced in high-dose rats and Low-dose rats. Serum BUN levels were significantly reduced in the Pre-H group (P < 0.05). Hypocalcaemia and hyperphos phataemia were detected in triangle grass (P < 0.05, P < 0.05). In addition, iPTH levels were significantly increased in the Pre-H group (P < 0.05). Alkaline phosphatase (ALP)levels were significantly decreased in the Pre-H group (P < 0.05). The bone mineral density was improved in the Pre-H and Pre-L groups. BMP-7 protein levels were significantly increased in the Pre-H group (P < 0.05). The pathological changes in muscle fibres in the thoracic aorta middle membranes were significantly alleviated in rats in the Pre-H and Pre-L groups. Changes in SM22α and SMα-act in protein levels were significantly attenuated in the Pre-H group (P < 0.05, P < 0.05). Changes in Runx2 and Osterix protein levels were also significantly attenuated in the Pre-H and Pre-L groups (P < 0.05, P < 0.05).
Triangle grass can simultaneously ameliorate vertebral bone loss and abnormal calcification in the thoracic aorta. Triangle grass has a definite effect on bone metabolism disorder in CKD-MBD rats.
三角草是百合科吊兰属多年生草本植物。它主要分布在中国的广东和广西两省。三角草的最初用途主要是治疗跌打损伤引起的骨痛和肿胀。三角草片(NO.Z20070544)也因其具有镇痛、抗炎、抗蛇毒、改善微循环等药理作用而被我院用作制剂(梅等,2006 年)。三角草片已广泛用于我院治疗慢性肾脏病-矿物质和骨异常(CKD-MBD)患者的骨痛。然而,三角草对慢性肾脏病合并矿物质和骨异常骨代谢的作用和机制尚不清楚。
本研究旨在探讨三角草汤对 CKD-MBD 大鼠骨代谢的影响。
采用 5/6 肾切除联合 0.5gNaHPO/大鼠建立 CKD-MBD 模型。采用自动生化分析仪测定血清血尿素氮(BUN)、肌酐(Cr)、磷(P)、钙(Ca)和全段甲状旁腺激素(iPTH)水平。采用 Viva CT 40 系统测定骨矿物质密度。采用 Western blot 分析测定骨形态发生蛋白 7(BMP-7)、 runt 相关转录因子 2(Runx2)和成骨细胞特异性转录因子 2(Osterix)蛋白水平。通过组织病理学和免疫组织化学(IHC)评估肾脏、椎体和胸主动脉组织样本。
高剂量组和低剂量组的膜增厚、坏死、肿胀和铸型沉积程度明显减轻。Pre-H 组血清 BUN 水平明显降低(P<0.05)。三角草中发现低钙血症和高磷血症(P<0.05,P<0.05)。此外,Pre-H 组 iPTH 水平明显升高(P<0.05)。碱性磷酸酶(ALP)水平在 Pre-H 组明显降低(P<0.05)。Pre-H 和 Pre-L 组的骨矿物质密度均有所提高。Pre-H 组 BMP-7 蛋白水平明显升高(P<0.05)。Pre-H 和 Pre-L 组大鼠胸主动脉中膜肌纤维的病理变化明显缓解。Pre-H 组 SM22α和 SMα-act 蛋白水平的变化明显减弱(P<0.05,P<0.05)。Pre-H 和 Pre-L 组 Runx2 和 Osterix 蛋白水平的变化也明显减弱(P<0.05,P<0.05)。
三角草可同时改善 CKD-MBD 大鼠的椎体骨丢失和胸主动脉异常钙化。三角草对 CKD-MBD 大鼠的骨代谢紊乱有明确的作用。