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脂肪幹細胞分泌之微囊泡改善環磷醯胺誘導之過動膀胱症

為了解決mast cells中文的問題，作者李孟哲 這樣論述：

膀胱是人體中重要器官之一，主要功能包含暫存尿液及排除含代謝廢物的尿液。隨著年齡增加，高齡人口表現膀胱過動症的比例也隨之遞增，考慮到生活品質降低和社會醫療成本增加，過動膀胱症是一個不可忽視的醫療議題。膀胱過動症為一種泌尿系統疾病，常見症狀如頻尿、尿急、儲尿功能下降，致病原因有很多，如糖尿病、下尿道阻塞、細菌感染以及尿路上皮受損，病 理 上 可 觀 察 到 逼 尿 肌 過度敏感 、 慢 性 發 炎 等 現 象 。 環 磷 醯 胺(Cyclophosphamide, CYP) 作為一種化療藥物，常在組織移植過程作為免疫抑制劑使用，在體內經過代謝後產生丙烯醛 (Acrolein)，經過腎臟濾出後順著

尿液經過膀胱，將對膀胱造成損傷形成出血性膀胱炎，因此使用環磷醯胺作為誘導過動膀胱症的藥物。目前對於過動膀胱症的治療藥物多半伴隨不適的副作用，往往降低病患服藥意願，脂肪幹細胞為脂肪組織中具有自我修復與增殖的細胞群，許多研究注重脂肪幹細胞應用於活體中的作用以及培養脂肪幹細胞時分泌之微囊泡或胞外體應用於實驗研究中。因為自體細胞移植產生較少的免疫排斥、較高的組織相容性等。先前研究已各別使用脂肪幹細胞與脂肪幹細胞分泌之微囊泡治療膀胱缺血大鼠模式，能有效改善大鼠頻尿、缺血、發炎等。本研究欲探討脂肪幹細胞分泌之微囊泡應用於 CYP 誘導出血性膀胱炎中是否具抑制膀胱過度活化以及抗發炎效果。實驗結果顯示脂肪幹細

胞分泌之微囊泡可下調減少第三型毒蕈鹼受體減少膀胱逼尿肌過度活化、減緩頻尿、過敏化的現象和以及下調減少 P2X7 受體表現量以及下游 Caspase 1、IL-1β等發炎路徑中相關分子的表現量，病理上觀察脂肪幹細胞所分泌之微囊泡可以降低免疫細胞浸潤現象、維持尿路上皮完整程度與抑制膀胱纖維化等結果。總結，脂肪幹細胞分泌之微囊泡可以改善CYP 引起之過動膀胱症。

探討 NS5806 抗急性發炎的機制

為了解決mast cells中文的問題，作者楊博喩 這樣論述：

Content中文摘要....................................................................................................................................iAbstract......................................................................................................................................iiContent ...

...................................................................................................................................iiiFigure Content ..........................................................................................................................viTable Content..............

...............................................................................................................viiiChapter 1: Introduction...............................................................................................................11.1 Inflammatory response ........................

.............................................................................11.2 Inflammatory pain ............................................................................................................21.3 MAPKs and inflammation.................................................................

...............................21.4 Kv4 channels ....................................................................................................................31.5 NS5806 ...........................................................................................................................

..31.6 Aim ...................................................................................................................................4Chapter 2: Materials and Methods..............................................................................................62.1 Animal ...................

...........................................................................................................62.2 Carrageenan-induced inflammation .................................................................................62.3 NS5806 ..............................................................

...............................................................62.4 PD98059 ...........................................................................................................................72.5 SP600125........................................................................................

..................................72.6 Tetrodotoxin (TTX)..........................................................................................................82.7 Behavioral tests ................................................................................................................82.

8 Tissue processing for immunohistochemistry ..................................................................92.9 Single antigen immunohistochemistry .............................................................................92.10 Double-fluorescence immunohistochemistry.........................

......................................102.11 Quantitation of immunoreactivity in the hindpaw skin ................................................ 112.12 Toluidine blue O staining .............................................................................................122.13 Hematoxylin and Eosi

n (H&E) staining.......................................................................122.14 Quantitation of pERK+ neurons and satellite glial cells in the DRG............................132.15 Quantification of immunofluorescence images............................................................13

v2.16 Statistics........................................................................................................................14Chapter 3: Results.....................................................................................................................143.1 Time-dependently anti

nociceptive effect of NS5806 in carrageenan-evokedinflammatory pain ............................................................................................................143.2 NS5806 reduces carrageenan-evoked mast cell degranulation in the paw skin.............153.3 NS5806 reduces the area of

footpad macrophages in carrageenan-evoked inflammatorypain ...................................................................................................................................163.4 NS5806 reduces carrageenan-evoked white blood cell infiltration in the paw skin ......163.5 NS5806 redu

ces carrageenan-elevated pERK in both peptidergic- and non-peptidergicSENFs in the paw skin .....................................................................................................173.6 NS5806 reduces carrageenan-activated neurons and satellite glial cells in the L4 DRG.................

.........................................................................................................................183.7 The effects of NS5806 on immune cells in the paw skin is indirectly ...........................183.8 NS5806 may have similar mechanisms with MEK inhibitor in vivo...........

..................193.8.1 Co-application of submaximal dosages of NS5806 and PD98059 has no additiveanalgesic effect in carrageenan-induced inflammatory pain ............................................193.8.2 Co-application of submaximal dosages of NS5806 and SP600125 has additiveanalgesic effect i

n carrageenan-induced inflammatory pain ............................................193.8.3 Co-application of submaximal dosages of NS5806 and SP600125 reducescarrageenan-induced edema .............................................................................................203.8.4 The anti-infla

mmatory dosage of NS5806 or PD98059 can retract peptidergic nervefibers in the subepidermis.................................................................................................203.9 NS5806 strongly reduces carrageenan-enhanced activity in Kv4.3+ DRG neurons ......21Chapter 4: Discussion.

..............................................................................................................214.1 NS5806 may act as a Kv4 activator and an ERK pathway inhibitor for the analgesiceffect .................................................................................................

................................224.2 The analgesic effect of local NS5806 may act as an ERK inhibitor ..............................234.3 NS5806 may act as an ERK pathway inhibitor to cause nerve fiber retraction .............234.4 The inhibitory effect of NS5806 on immune cell activation and infil

tration is indirectly..........................................................................................................................................244.5 Possible target of NS5806 in the dermis of rat hindpaw ................................................244.6 Possible mechanisms underl

ying the acute anti-inflammatory effect of NS5806..........25vi4.7 Future prospects..............................................................................................................25References ..............................................................................................

..................................26Figures ......................................................................................................................................31Tables..................................................................................................................

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