胰岛素样生长因子结合蛋白相关蛋白1对SD大鼠和比格犬肾组织的影响及意义

doi:10.3877/cma.j.issn.2095-2015.2017.01.006

中华消化病与影像杂志(电子版) ›› 2017, Vol. 07 ›› Issue (01) : 26 -33. doi: 10.3877/cma.j.issn.2095-2015.2017.01.006

所属专题：文献；

基础研究

胰岛素样生长因子结合蛋白相关蛋白1对SD大鼠和比格犬肾组织的影响及意义

管宇¹, 刘立新²^,^†(

), 郭钰¹, 吕婷婷¹, 郭晓红³, 郭亚荣¹

^1. 030001　太原，山西医科大学第一医院消化科在读研究生
^2. 030001　太原，山西医科大学第一医院科研实验中心；030001　太原，山西医科大学第一医院消化科
^3. 030001　太原，山西医科大学第一医院科研实验中心

收稿日期:2016-10-17 出版日期:2017-02-01
通信作者: 刘立新
基金资助:
山西省重点研发计划项目（国际合作）(201603D421023)

Effect and significance of IGFBPrP1 on kidney tissues in SD rats and beagles

Yu Guan¹, Lixin Liu²^,^†(), Yu Guo¹, Tingting Lyu¹, Xiaohong Guo³, Yarong Guo¹

^1. Postgraduate Student of Department of Gastroenterology, First Hospital of Shanxi Medical University, Taiyuan 030001, China
^2. Experimental Center of Science and Research, First Hospital of Shanxi Medical University, Taiyuan 030001, China; Department of Gastroenterology, First Hospital of Shanxi Medical University, Taiyuan 030001, China
^3. Experimental Center of Science and Research, First Hospital of Shanxi Medical University, Taiyuan 030001, China

Received:2016-10-17 Published:2017-02-01
Corresponding author: Lixin Liu
About author:
Corresponding author: Liu Lixin, Email: lixinliu6@ hotmail.com

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管宇, 刘立新, 郭钰, 吕婷婷, 郭晓红, 郭亚荣. 胰岛素样生长因子结合蛋白相关蛋白1对SD大鼠和比格犬肾组织的影响及意义[J/OL]. 中华消化病与影像杂志(电子版), 2017, 07(01): 26-33.

Yu Guan, Lixin Liu, Yu Guo, Tingting Lyu, Xiaohong Guo, Yarong Guo. Effect and significance of IGFBPrP1 on kidney tissues in SD rats and beagles[J/OL]. Chinese Journal of Digestion and Medical Imageology(Electronic Edition), 2017, 07(01): 26-33.

目的

研究胰岛素样生长因子结合蛋白相关蛋白1(IGFBPrP1)对SD大鼠和比格犬肾组织的影响及意义。

方法

(1)健康雄性SD大鼠随机分为3组，A组：经尾静脉注射生理盐水；B组：经尾静脉注射腺病毒携带增强型绿色荧光蛋白(Ad-EGFP)；C组：经尾静脉注射腺病毒携带IGFBPrP1(Ad-IGFBPrP1)。各组于注射后1、2、4、6、9周留取肾组织。(2)健康雄性比格犬随机分为3组，D组：正常饲养；E组：皮下注射硫代乙酰胺(TAA)；F组：皮下注射TAA，5周起协同注射IGFBPrP1抗体。各组于12周留取肾组织。HE和Sirius red染色观察SD大鼠和比格犬肾组织形态结构改变和胶原纤维沉积情况；免疫组织化学染色检测SD大鼠肾组织IGFBPrP1、白细胞介素1β(IL-1β)、转化生长因子β1(TGFβ1)、纤维连接蛋白(Fn)以及比格犬肾组织IGFBPrP1的分布和表达情况。

结果

(1)SD大鼠：与A组和B组正常肾组织相比，C组肾组织病理学改变逐渐加重，胶原纤维含量逐渐增多；IGFBPrP1自转染后1周开始增多，2周达高峰，后逐渐减弱；IL-1β于6周达高峰，9周下降；TGFβ1呈时间按依赖性持续升高，9周达高峰；Fn在9周时显著增多。(2)比格犬：与D组正常肾组织相比，E组肾组织病变显著，胶原纤维含量增多，而F组较E组病变明显改善；E组IGFBPrP1表达增强，F组较E组减弱。

结论

IGFBPrP1对肾组织会造成不同程度的损伤，是一种具有非组织特异性的致病因子。

关键词: 胰岛素样生长因子结合蛋白相关蛋白1, 肾, 大鼠，Sprague-Dawley, 比格犬

Objective

To investigate the effect and significance of insulin-like growth factor binding protein-related protein1(IGFBPrP1)on kidney tissues in SD rats and beagles.

Methods

(1)Healthy male SD rats were randomly divided into A, B and C group.Rats were respectively injected with the same doses of saline, adenovirus carrying enhanced green fluorescent protein(Ad-EGFP)and Ad-IGFBPrP1 via the tail vein.Kidney tissues were obtained for analysis at week 1, 2, 4, 6 and 9.(2)Healthy male beagles were randomly divided into D, E and F group.Beagles in D group were normally fed.Beagles in E group were treated with subcutaneous injection of thioacetamide(TAA). Beagles in F group were simultaneously given Anti-IGFBPrP1 antibody after 5 weeks with the treatment of TAA.Kidney tissues were obtained for analysis at 12 weeks.Histological changes and deposition of collagen in rats and beagles kidney tissues were evaluated by HE and Sirius red staining.Immunohistochemistry was used to analyze the expressions of IGFBPrP1, interleukin-1β(IL-1β), transforming growth factor-β1(TGF-β1)and fibronectin(Fn)in rats kidney tissues and IGFBPrP1 in beagles.

Results

(1)SD rats: Along with the prolongation of the time, the lesion gradually aggravated and the content of collagen fibers gradually increased in C group comparing with A and B group.In C group, the protein level of IGFBPrP1 increased 1 week after transfection and peaked at 2 weeks after the injection, and then gradually decreased.The expression of IL-1βpeaked at 6 weeks, and later downregulated.The level of TGFβ1 increased in a time-dependent manner and peaked at 9 weeks.Fn markedly upregulated at 9 weeks after injection.(2)Beagles: Compared with D group, obvious pathological changes and collagen fibers deposition were observed in E group.In F group, the lesion in kidney tissue ameliorated.IGFBPrP1 protein level was significantly increased in E group and that was downregulated in F group.

Conclusion

The kidney can be effected to one degree or another by IGFBPrP1, which is a non-tissue-specificity pathogenic factor.

Key words: Insulin-like growth factor binding protein-related protein 1, Kidney, Rats, Sprague-Dawley, Beagles

图1 SD大鼠肾组织HE染色(×200)

图2 SD大鼠肾组织Sirius red染色(×200)

表1 SD大鼠肾组织胶原纤维阳性面积百分比(经平方根反正弦转换，±s)

组别	n	胶原纤维阳性面积百分比
A组	10	0.18±0.03
B组	25	0.18±0.02
C组(1周)	5	0.19±0.06
C组(2周)	5	0.20±0.09
C组(4周)	5	0.21±0.07
C组(6周)	5	0.23±0.08
C组(9周)	5	0.28±0.10^a

表1 SD大鼠肾组织胶原纤维阳性面积百分比(经平方根反正弦转换，±s)

组别	n	胶原纤维阳性面积百分比
A组	10	0.18±0.03
B组	25	0.18±0.02
C组(1周)	5	0.19±0.06
C组(2周)	5	0.20±0.09
C组(4周)	5	0.21±0.07
C组(6周)	5	0.23±0.08
C组(9周)	5	0.28±0.10^a

图3 SD大鼠肾组织胰岛素样生长因子结合蛋白相关蛋白1(IGFBPrP1)染色(×400)

图4 SD大鼠肾组织白细胞介素1β(IL-1β)染色(×400)

图5 SD大鼠肾组织转化生长因子β1(TGFβ1)染色(×400)

图6 SD大鼠肾组织纤维连接蛋白(Fn)染色(×400)

表2 SD大鼠肾组织免疫组织化学染色图像半定量分析结果(IOD×10⁴，±s)

组别	n	IGFBPrP1	IL-1β	TGFβ1	Fn
A组	10	0.65±0.09	0.19±0.04	0.57±0.07	0.37±0.05
B组	25	0.68±0.08	0.20±0.05	0.58±0.06	0.36±0.04
C组(1周)	5	3.12±0.40^a	0.46±0.05^b	0.91±0.10	0.37±0.04
C组(2周)	5	4.55±0.78^a	0.73±0.08^a	1.98±0.33^a	0.38±0.05
C组(4周)	5	3.15±0.63^a	1.66±0.14^a	2.52±0.42^a	0.39±0.04
C组(6周)	5	1.23±0.08	1.93±0.15^a	3.14±0.59^a	0.41±0.07
C组(9周)	5	0.66±0.06	0.86±0.09^a	3.64±0.71^a	0.60±0.07^a

表2 SD大鼠肾组织免疫组织化学染色图像半定量分析结果(IOD×10⁴，±s)

组别	n	IGFBPrP1	IL-1β	TGFβ1	Fn
A组	10	0.65±0.09	0.19±0.04	0.57±0.07	0.37±0.05
B组	25	0.68±0.08	0.20±0.05	0.58±0.06	0.36±0.04
C组(1周)	5	3.12±0.40^a	0.46±0.05^b	0.91±0.10	0.37±0.04
C组(2周)	5	4.55±0.78^a	0.73±0.08^a	1.98±0.33^a	0.38±0.05
C组(4周)	5	3.15±0.63^a	1.66±0.14^a	2.52±0.42^a	0.39±0.04
C组(6周)	5	1.23±0.08	1.93±0.15^a	3.14±0.59^a	0.41±0.07
C组(9周)	5	0.66±0.06	0.86±0.09^a	3.64±0.71^a	0.60±0.07^a

图7 比格犬肾组织HE染色(×200)

图8 比格犬肾组织Sirius red染色(×200)

表3 比格犬肾组织胶原纤维阳性面积百分比(经平方根反正弦转换，±s)

组别	n	胶原纤维阳性面积百分比
D组	6	0.21±0.05
E组	6	0.29±0.10^a
F组	6	0.24±0.08^bc

表3 比格犬肾组织胶原纤维阳性面积百分比(经平方根反正弦转换，±s)

组别	n	胶原纤维阳性面积百分比
D组	6	0.21±0.05
E组	6	0.29±0.10^a
F组	6	0.24±0.08^bc

图9 比格犬肾组织胰岛素样生长因子结合蛋白相关蛋白1(IGFBPrP1)染色(×400)

表4 比格犬肾组织免疫组织化学染色图像半定量分析结果(IOD×10⁴，±s)

组别	n	胰岛素样生长因子结合蛋白相关蛋白1(IGFBPrP1)
D组	6	0.90±0.12
E组	6	3.99±0.59^a
F组	6	2.15±0.11^ab

表4 比格犬肾组织免疫组织化学染色图像半定量分析结果(IOD×10⁴，±s)

组别	n	胰岛素样生长因子结合蛋白相关蛋白1(IGFBPrP1)
D组	6	0.90±0.12
E组	6	3.99±0.59^a
F组	6	2.15±0.11^ab

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