Murphey E D, Chattopadhyay N, Bai M, Kifor O, Harper D, Traber D L, Hawkins H K, Brown E M, Klein G L
Department of Anesthesia, University of Texas Medical Branch and Shriners Burns Hospital, Galveston 77555-0362, USA.
Crit Care Med. 2000 Dec;28(12):3885-90. doi: 10.1097/00003246-200012000-00024.
To test the hypothesis that the hypocalcemia and hypoparathyroidism that follow severe burn injury are related to up-regulation of the parathyroid gland calcium-sensing receptor (CaR), which may reduce the set-point for suppression of circulating parathyroid hormone by blood calcium.
A controlled but unblinded study.
An investigational intensive care unit.
Female range ewes.
Sheep were subjected to a 40% total body surface area burn under anesthesia (n = 9) or sham burn receiving anesthesia and fluid resuscitation only (n = 8) and were killed 48 hrs postburn.
Blood ionized calcium, magnesium, and creatinine, and urinary calcium, magnesium, and creatinine were monitored for 48 hrs. After the sheep were killed, parathyroids (burn group, n = 3; sham group, n = 4) and kidneys (n = 4, each group) were harvested, snap frozen in liquid nitrogen, and analyzed for CaR messenger ribonucleic acid (mRNA) by Northern blot, and were analyzed for CaR cell-surface staining by immunocytochemistry with a polyclonal CaR-specific antiserum (parathyroids only). Bumed sheep were hypocalcemic and hypomagnesemic compared with sham-burned control sheep. CaR mRNA was increased by 50% (p < 0.005, analysis of variance) with a corresponding increase in the intensity of CaR immunoreactivity associated with the cell surface in parathyroids obtained from burned (n = 3) compared with sham-burned (n = 2) sheep. These findings are consistent with up-regulation of the parathyroid CaR and a related decrease in set-point for calcium suppression of parathyroid hormone secretion that may contribute to the previously reported postburn hypoparathyroidism and hypocalcemia.
验证以下假设,即严重烧伤后发生的低钙血症和甲状旁腺功能减退与甲状旁腺钙敏感受体(CaR)上调有关,这可能会降低血钙对循环中甲状旁腺激素抑制作用的设定点。
一项非盲对照研究。
一个研究性重症监护病房。
雌性成年母羊。
绵羊在麻醉状态下接受40%体表面积烧伤(n = 9),或仅接受麻醉和液体复苏的假烧伤(n = 8),并在烧伤后48小时处死。
监测48小时内的血离子钙、镁和肌酐,以及尿钙、镁和肌酐。绵羊处死后,采集甲状旁腺(烧伤组,n = 3;假烧伤组,n = 4)和肾脏(每组n = 4),在液氮中速冻,通过Northern印迹法分析CaR信使核糖核酸(mRNA),并用多克隆CaR特异性抗血清通过免疫细胞化学法分析甲状旁腺(仅甲状旁腺)的CaR细胞表面染色。与假烧伤对照绵羊相比,烧伤绵羊出现低钙血症和低镁血症。与假烧伤(n = 2)绵羊相比,烧伤(n = 3)绵羊甲状旁腺中CaR mRNA增加了50%(方差分析,p < 0.005),同时与细胞表面相关的CaR免疫反应强度相应增加。这些发现与甲状旁腺CaR上调以及甲状旁腺激素分泌的钙抑制设定点相关降低一致,这可能导致先前报道的烧伤后甲状旁腺功能减退和低钙血症。