貝他一型轉型生長因子對犬蛔蟲症腎臟損傷與纖維化之分子致病機轉

Molecular pathogenesis of TFG-β1 on kidney injury and fibrosis of toxocariasis

雲筱涵(Hsiao-Han Yun)

指導教授 ： 范家堃

臺北醫學大學/醫學院/醫學科學研究所/碩士(2014年)

摘要

犬蛔蟲(Toxocara canis)為一種人畜共通寄生蟲(zoonotic parasite)，人類若是誤食了犬蛔蟲的感染性蟲卵後，蟲卵會在人體小腸內孵化成幼蟲，因不會發育成成蟲，幼蟲穿過腸壁，隨血液在宿主體內移行，進而造成內臟幼蟲移行症(visceral larva migras)，若是幼蟲移行至腎臟，可能造成腎臟的損傷及發炎。研究中指出，犬蛔蟲幼蟲移行至小鼠的肝臟肌肉或是腦部等器官導致肉芽腫發炎性反應，並發現Transforming growth factor-β1(TGF-β1)表現增強，另有許多研究中指出，TGF-β1在腎臟發炎或纖維化病變中扮演重要的角色。本實驗利用LSKL可抑制TFG-β1表現之特性，及SLLK作為無效抑制組，每天2次腹腔注射至感染小鼠(2.5μg/g-weight) ，於感染後3天到8週，摘取小鼠腎臟，經由西方墨點法(western blot)及免疫組織化學染色法 (Immunohistochemical staining)，探討TGF-β1、Proliferating Cell Nuclear Antigen (PCNA)、Connective tissue growth factor (CTGF)、Alpha Smooth Muscle Actin (α-SMA)、Endothelin-1 (ET-1)在犬蛔蟲性腎炎的表現情形。由Western blot的結果顯示，受到犬蛔蟲感染的小鼠，藉由LSKL降低TGF-β1的表現，相較於感染組及SLLK的組別，發炎現象與TGF-β1、PCNA、CTGF、α-SMA、ET-1在感染一週及八週中有減緩的趨勢。

關鍵字

犬蛔蟲 ； 犬蛔蟲症 ； 腎臟 ； 貝他一型轉型生長因子 ； 結締組織生長因子 ； 平滑肌α-肌動蛋白 ； 內皮素

並列摘要

Human beings are one of paratenic hosts of Toxocara canis. When people accidentally got infection by T. canis embryonated eggs, T. canis larvae may migrate in the body thus leading to visceral larva migrans. Some studies have indicated that enhanced expression of transforming growth factor-β1(TGF-β1) were found during larval invasion of small intestine, liver, muscle, and brain of T. canis-infected mice. Substantial studies have indicated that TGF-β1 play an important role in kidney injury and fibrosis. Since TGF-β1 is supposed a deleterious cytokine in toxocariasis, we hypothesize that inhibition of TGF-β1 expression will benefit to reduce the severity of the kidney injury. Present study intends to explore the role of TGF-β1 in damage of T. canis-infected mice kidney. Kidney damage associated biomarkers (KDAB) including TGF-β1, proliferating cell nuclear antigen (PCNA), connective tissue growth factor (CTGF), endothelin-1 (ET-1), and alpha smooth muscle actin (α-SMA) in the kidney were assessed by inhibition of TGF-β1 expression using peptide inhibitor (LSKL) via peritoneal injection twice (2.5μg/g-weight) per day. The techniques of immunohistochemistry and western blotting were utilized to insight into the molecular pathogenesis of TGF-β1 involved in regulation of those KDAB involved in kidney damage in toxocariasis. Results indicated that when TGF-β1 expression was reduced, the kidney injury was lessened in LSKL-treated mice as supposedly due to reduced PCNA, CTGF, α-SMA and ET-1 expressions as compared to those in SLLK-treated or infection mice.

並列關鍵字

Toxocara canis ； Toxocarasis ； kidney ； TFG-β1 ； CTGF ； α-SMA ； ET-1

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