【摘要】：目的： 膠囊滲透壓泵植入野生型小鼠皮下并持續(xù)恒量釋放重組鼠胰島素樣生長因子結合蛋白相關蛋白1 (rmIGFBPrP1),觀察小鼠肝腎組織纖維化相關指標的表達情況,探討rmIGFBPrP1對小鼠肝腎組織的影響及其可能的意義。 方法： 將26只雄性C57BL/6野生型小鼠按隨機數(shù)字表法分為3組：正常對照組(8只),常規(guī)飲食持續(xù)4周；假手術組(8只),背部僅做一橫向切口,縫合,常規(guī)飲食持續(xù)4周；模型組(10只),用1%水合氯醛麻醉小鼠,于小鼠前腿之間后背部行一0.5厘米左右橫切口。用組織鉗由切口處皮下向小鼠尾部方向撐出一個膠囊大小的空間,空間應大到膠囊泵體可以有一點移動,但不能讓泵體輕易滑到小鼠側翼去。行手術植入注滿rmIGFBPrP1溶液的膠囊滲透壓泵,輸藥管釋出口要朝內塞入皮下,不可反向以致釋出口剛好在傷口之下。膠囊泵連續(xù)恒定釋放100μg/ml rmIGFBPrP1溶液,泵容積90μl,泵速0.11μl/h,持續(xù)4周。4周末處死各組小鼠,采集肝腎組織。HE染色和飽和苦味酸-天狼星紅染色觀察肝腎組織形態(tài)學改變及膠原沉積情況；免疫組織化學染色檢測肝腎組織中IGFBPrP1、Smad3、p-Smad2/3和Ⅲ型膠原(CollagenⅢ)的表達和分布；原位末端轉移酶標記法(TUNEL)檢測肝細胞凋亡情況。 結果： 與對照組和假手術組相比,模型組肝組織中膠原纖維含量增多,IGFBPrP1、Smad3 p-Smad2/3、CollagenⅢ表達增強(P0.01)。模型組腎組織中僅IGFBPrP1表達較對照組和假手術組有所增強,膠原纖維和其它指標表達未見差異(P0.05)。TUNEL結果顯示模型組肝細胞凋亡數(shù)目增多,與正常組和假手術組相比,差異有統(tǒng)計學意義(P0.01)。 結論： 1.外源性IGFBPrP1可促進小鼠肝細胞凋亡和肝纖維化的形成,而對小鼠腎組織影響甚微。 2. IGFBPrP1致小鼠臟器組織纖維化可能具有選擇性。
[Abstract]:Objective: to investigate the expression of insulin like growth factor binding protein-associated protein 1 (rmIGFBPrP1) in mice by osmotic pump implantation into the subcutaneous of wild-type mice, and to observe the expression of insulin like growth factor binding protein-associated protein 1 (rmIGFBPrP1) in mice liver and kidney tissues. To investigate the effect of rmIGFBPrP1 on the liver and kidney of mice and its possible significance. Methods: 26 male C57BL/6 wild-type mice were randomly divided into three groups: normal control group (n = 8), sham operation group (n = 8) and sham operation group (n = 8). In the model group (n = 10), 1% chloral hydrate was used to anesthetize mice, and a 0.5 cm transverse incision was performed on the back of the front leg of the mice. Using tissue forceps from the incision subcutaneously to the tail of the mouse to open a capsule space, the space should be so large that the capsule pump body can move a little, but can not let the pump body slide to the mouse flank easily. The capsule osmotic pump filled with rmIGFBPrP1 solution was implanted surgically. The release outlet of the drug delivery tube should be inserted subcutaneously into the skin, so that the release outlet was just under the wound. The capsule pump continuously released 100 渭 g/ml rmIGFBPrP1 solution, pump volume 90 渭 l and pump velocity 0.11 渭 l / h. The mice were killed for 4 weeks at the end of 4 weeks. The liver and kidney tissues were stained with HE and saturated picric acid-Sirius red staining to observe the changes of liver and kidney morphology and collagen deposition. Immunohistochemical staining was used to detect the expression and distribution of IGFBPrP1Smad3 p-Smad2 / 3 and type 鈪，

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