Change in Expression of the Guanosine Triphosphate Cyclohydrolase I in LPS-stimulated Rats is Tissue Specific

GTPCH之表現於酯多醣內刺激之大白鼠身上具組織專一性

洪育均(Yu-Chun Hung) ； 蔡佩珊(Pei-Shan Tsai) ； 黃俊仁(Chun-Jen Huang) ； 楊志東(Stone Yang) ； 謝敏琪(Min-Chi Hsieh) ； Jeffrey W. Skimming

《Acta Anaesthesiologica Taiwanica》 42卷1期 (2004/03) Pp. 23-31

摘要

背景：過去文獻顯示tetrahydrobioptin（BH4）是調控 iNOS 活性所需之因素，而 BH4 之合成則受到 GTPCH 之調控；過去文獻顯示 GTPCH 會與 iNOS 共同被酯多醣內毒素所誘導產生。然而，吾人在一利用酯多內毒素刺激巨噬細胞引發敗血症的研究中發現 GTPCH 表現是經常而非誘發性；這數據與過去相關文獻報導之結果不同。未進一步澄清敗血症對 GTPCH 表現之影響，吾人於是進行了以下以酯多醣內毒素刺激導致敗血症之動物實驗，來探討老鼠肺、肝及腎臟GTPCH 之表現。
方法：大白鼠隨機接受生理食鹽水或酯多醣內毒素之注射，於注射後吾人分別在零、一、二、三及四小時後分別犧牲大白鼠，而收集之急進冷陳檢體則以RT-PCR 檢驗分析遙二量組織中 GTPCH 之濃度。
結果：吾人發現兩組大白鼠的肺臟及肝臟之 GTPCH mRNA 濃度相近，此數據顯示大白鼠的肺臟及肝臟之 GTPCH 表現是經常而非誘發性的；然而，相較於肺、肝之數據，吾人發現大白鼠腎臟之 GTPCH 表現是誘發性的，而酯多醣內毒素會誘發腎臟之 GTPCH 表現。
結論：GTPCH 表現具有組織專一性，不同組織對敗血症刺激所造成之 GTPCH 表現反應不同，因此以調控 GTPCH 表現來抑制一氧化氮過度一之療法，應針對各組織之差異而加以調整。

關鍵字

Nitric oxide synthase ； GTP cyclohydrolase ； 大白鼠 ； 酯多糖 ； 敗血症 ； 肺臟 ； 肝臟 ； 腎臟

並列摘要

Background: The synthesis of tetrahydrobiopterin (BH4), a necessary cofactor for inducible nitric oxide synthase (iNOS), had been reported to be controlled by guanosine triphosphate cyclohydrolase I (GTPCH). Previous studies have demonstrated that GTPCH was induced by bacterial toxin. However, in a study using lipopolysaccharide (LPS)-treated murine macrophages model, we found that GTPCH expression was in fact constitutive rather than inducible. To further elucidate the effects of endotoxemia on GTPCH expression, we therefore preformed this LPS-treated rodent endotoxemia study with special focus on lung, liver, and kidney.
Methods: Rats randomly received either normal saline (N/S) or LPS injection. At five different time points (0, 1, 2, 3 and 4 h after LPS injection in LPS group and comparable time points in N/S group), four rats from each group were sacrificed. Snap frozen tissues were then analyzed using semi-quantitative RT-PCR to determine GTPCH mRNA concentrations.
Results: GTPCH mRNA concentrations in lung and liver tissues were similar between groups. On the other hand, GTPCH mRNA concentrations in renal tissues were significantly higher in the LPS group as compared with the N/S group. Our data demonstrated that GTPCH expression in lung and liver tissues was constitutive rather than inducible, whereas renal GTPCH expression was induced by LPS in a time-dependent manner.
Conclusions: GTPCH expression is tissue specific. Different tissues react differently to endotoxemia in terms of GTPCH expression. Therefore, efforts aiming at modulating GTPCH expression to limit NO overproduction should adjust accordingly.

並列關鍵字

Nitric oxide synthase ； GTP cyclohydrolase ； Rats ； Lipopolysaccharides ； Sepsis ； Lung ； Liver ； Kidney