Effects of hemin on heme oxygenase-1, gastric emptying, and symptoms in diabetic gastroparesis.
Effects of hemin on heme oxygenase-1, gastric emptying, and symptoms in diabetic gastroparesis.
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DOI：
10.1111/nmo.12874
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发表时间：
2016-11
影响因子：
3.5
通讯作者：
Zinsmeister AR
中科院分区：
文献类型：
--
作者：
Bharucha AE;Daley SL;Low PA;Gibbons SJ;Choi KM;Camilleri M;Saw JJ;Farrugia G;Zinsmeister AR
糖尿病胃轻瘫的治疗选择有限。血红素氧合酶（HO 1）的上调不能维持，导致Cajal间质细胞的损失和非肥胖糖尿病（NOD）小鼠胃排空延迟。我们的假设是，血红素上调HO 1将恢复正常的胃排空胃轻瘫的人。比较氯化血红素和安慰剂输注对糖尿病胃轻瘫患者HO 1活性和蛋白质、胃排空、自主神经功能和胃肠道症状的影响。在一项单中心、双盲、安慰剂对照、随机临床试验中，我们在20例年龄为41±5（SEM）岁的糖尿病胃轻瘫患者中比较了静脉注射氯化血红素（在白蛋白中制备）或单用白蛋白（安慰剂）。第1、3和7天输注后，每周输注一次，再持续7周。评估包括HO 1蛋白和酶活性水平的血液检测、13 C-螺旋藻呼气试验的胃排空、自主神经功能（基线和结束）以及每2周一次的胃肠道症状。随机分配至氯化血红素组的11例患者中有9例完成了所有研究程序。与安慰剂相比，氯化血红素在第3天（P= 0.0002）和第7天（P= 0.008）增加了HO 1蛋白，在第3天（P= 0.0003）增加了HO 1活性，但之后没有。与安慰剂组相比，氯化血红素组的胃排空、自主神经功能和症状没有显著差异。氯化血红素未能维持超过一周的HO 1水平增加，并没有改善胃排空或糖尿病胃轻瘫的症状。进一步的研究是必要的，以确定是否更频繁的氯化血红素输注或其他药物将有更持久的影响HO 1和改善胃排空。
Therapeutic options for management of diabetic gastroparesis are limited. Failure to maintain upregulation of heme oxygenase (HO1) leads to loss of interstitial cells of Cajal and delayed gastric emptying in non-obese diabetic (NOD) mice. Our hypothesis was that hemin upregulation of HO1 would restore normal gastric emptying in humans with gastroparesis. To compare effects of hemin and placebo infusions on HO1 activity and protein, gastric emptying, autonomic function, and gastrointestinal symptoms in diabetic gastroparesis. In a single-center, double-blind, placebo-controlled, randomized clinical trial, we compared intravenous hemin, prepared in albumin, or albumin alone (placebo) in 20 patients, aged 41±5 (SEM) years with diabetic gastroparesis. After infusions on days 1, 3, and 7, weekly infusions were administered for 7 additional weeks. Assessments included blood tests for HO1 protein and enzyme activity levels, gastric emptying with 13C-spirulina breath test, autonomic functions (baseline and end), and gastrointestinal symptoms every 2 weeks. Nine of 11 patients randomized to hemin completed all study procedures. Compared to placebo, hemin increased HO1 protein on days 3 (P=.0002) and 7 (P=.008) and HO1 activity on day 3 (P=.0003) but not after. Gastric emptying, autonomic functions, and symptoms did not differ significantly in the hemin group relative to placebo. Hemin failed to sustain increased HO1 levels beyond a week and did not improve gastric emptying or symptoms in diabetic gastroparesis. Further studies are necessary to ascertain whether more frequent hemin infusions or other drugs would have a more sustained effect on HO1 and improve gastric emptying.
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影响因子：
3.5
作者：
Grover M;Bernard CE;Pasricha PJ;Lurken MS;Faussone-Pellegrini MS;Smyrk TC;Parkman HP;Abell TL;Snape WJ;Hasler WL;McCallum RW;Nguyen L;Koch KL;Calles J;Lee L;Tonascia J;Ünalp-Arida A;Hamilton FA;Farrugia G;NIDDK Gastroparesis Clinical Research Consortium (GpCRC)
通讯作者：
NIDDK Gastroparesis Clinical Research Consortium (GpCRC)
影响因子：
6.7
作者：
通讯作者：
--
影响因子：
6.2
作者：
Dellon, ES;Szczepiorkowski, ZM;Chung, RT
通讯作者：
Chung, RT
影响因子：
3.5
作者：
Camilleri M;Iturrino J;Bharucha AE;Burton D;Shin A;Jeong ID;Zinsmeister AR
通讯作者：
Zinsmeister AR
影响因子：
3.5
作者：
Bharucha, Adil E.;Choi, Kyoung Moo;Zinsmeister, Alan R.
通讯作者：
Zinsmeister, Alan R.