摘要
目的 观察高盐饮食后钙调控网络的整体变化,探讨补充活性维生素D对高盐饮食引起的钙稳态失衡和骨代谢异常的作用.方法 24 只3 月龄雄性SD大鼠随机分对照组(Con)、高盐饮食组(HN)、对照+活性维生素D组(Con+VD)和高盐+活性维生素D组(HN+VD),每组6 只.干预4 周后,观察并比较各组大鼠的体质量、收缩压、24h尿量、血尿电解质、肾功能、血管紧张素-Ⅱ、醛固酮、心房钠尿肽、甲状旁腺激素(PTH)、成纤维细胞生长因子23、25-羟化维生素D、Ⅰ型原胶原前肽(PINP)及Ⅱ型胶原交联C-末端肽(CTX-Ⅱ)水平.采用Masson、PAS染色评估肾脏病理,免疫组化染色分析肾脏1α-羟化酶(CYP27B1)和24-羟化酶(CYP24A1)表达.结果 与Con组相比,HN组尿钙/肌酐、血PTH、血PINP和血CTX-Ⅱ水平较高,差异有统计学意义(P<0.05);HN组CYP27B1 表达下调,CYP24A1 表达上调,骨小梁减少.与HN组相比,HN+VD组血PTH、血PINP和血CTX-Ⅱ水平较低,差异有统计学意义(P<0.05);HN+VD组骨小梁增多.结论 高盐饮食可以抑制活性维生素D合成,升高PTH水平,影响钙稳态和骨代谢,补充活性维生素D一定程度改善这些影响.
Abstract
Objective To observe the overall changes in the calcium regulatory network after a high salt diet,and ex-plore the effects of supplementing with active vitamin D on calcium homeostasis imbalance and bone metabolism abnormalities caused by a high salt diet.Methods 24 3-month-old male SD rats were randomly divided into control group(Con),high-salt diet group(HN),control+active vitamin D group(Con+VD)and high-salt+active vitamin D group(HN+VD),with 6 rats in each group.After 4 weeks of intervention,the body weight,systolic blood pressure,24 h urine volume,blood and urine electrolytes,kidney function,and the levels of serum angiotensin Ⅱ,aldosterone,atrial natriuretic peptide,parathyroid hor-mone(PTH),fibroblast growth factor 23,25-hydroxyvitamin D,type I procollagen N-terminal pro-peptide(PINP),C-termi-nal cross-linked telopeptide of type Ⅱ collagen(CTX-Ⅱ)were determined and compared.Renal pathology was evaluated by Masson and PAS staining,and the expressions of cytochrome P450 family 27 subfamily B member 1(CYP27B1)and cyto-chrome P450 family 24 subfamily A member 1(CYP24A1)in kidney were analyzed by immunohistochemical staining.Results Compared with the Con group,the HN group had higher levels of urinary calcium/creatinine,serum PTH,PINP and CTX-Ⅱ,with statistical significance(P<0.05);CYP27B1 expression was down-regulated,CYP24A1 expression was up-reg-ulated,and bone trabeculae decreased in the HN group.Compared with the HN group,the HN+VD group had lower levels of serum PTH,PINP and CTX-Ⅱ,and the differences were statistically significant(P<0.05);the bone trabeculae increased in the HN+VD group.Conclusion A high-salt diet can inhibit the synthesis of active vitamin D,increase PTH level,affect cal-cium homeostasis and bone metabolism.Supplementation with active vitamin D can ameliorate these effects to some extent.
基金项目
国家重点研发计划(2020YFC2005000)
国家重点研发计划(2021YFC2500202)
上海市科委科技创新行动计划(20Y11904500)
上海市科委科技创新行动计划(21ZR1411100)