本文選題：程序性控制 + 血管內皮功能　； 參考：《福建醫(yī)科大學》2013年碩士論文

【摘要】：背景煙草暴露與心血管疾病有關聯(lián)，尼古丁是煙草中最主要的致病成分。生命發(fā)育早期的環(huán)境與母體等因素可在胚胎期形成印痕，程序性控制出生后甚至成年期心血管疾病的發(fā)生。血管內皮功能損傷和胰島素樣生長因子(insulin likegrowth factors，IGFs)軸異常參與介導心血管疾病發(fā)生發(fā)展。目前還不清楚孕婦尼古丁暴露對日后成年期子代血管內皮功能和IGFs軸的影響。 目的本研究旨在明確產前尼古丁暴露（Prenatal Nicotine Exposure, PNE）對子代大鼠血管內皮功能和IGFs軸的影響及其潛在的性別依賴性差異、并闡明這些效應是否可持續(xù)作用至日后成年期。 方法孕SD大鼠20只隨機分成兩組：PNE組和正常對照組，均予皮下植入滲透微泵（2ML4型），其中PNE組滲透微泵攜帶尼古丁(8mg/kg/day)，正常對照組滲透微泵僅攜帶生理鹽水。待子代大鼠滿5月齡時，腹腔麻醉，迅速截取胸主動脈及腸系膜動脈各4mm，采用Power Lab數據采集分析系統(tǒng)測定血管內皮功能；收集血樣，采用ELISA酶聯(lián)免疫法測定血清IGF-1、 IGF-2、 IGFBP-1、IGFBP-2及IGFBP-3水平；取胸主動脈、心、肺、肝、腎、胰腺等組織標本，行HE染色及免疫組化染色檢測IGF-1、IGF-1R、IGF-2、IGFBP-1、IGFBP-2及IGFBP-3的組織特異性表達水平。 結果 1) Ach與SNP誘導的子代大鼠胸主動脈內皮依賴/非依賴性血管舒張百分數，PNE組與正常對照組之間無顯著差異（均P＞0.05）； 2) Ach與SNP誘導的子代大鼠腸系膜動脈的內皮依賴/非依賴性血管舒張百分數， PNE組雄性子代較正常對照組顯著降低（P＜0.05），而雌性子代較正常對照組顯著升高（P＜0.05）； 3)子代大鼠胸主動脈組織HE染色可見管腔不平、內皮細胞空泡變性、內皮部分脫落、內膜增厚，中膜平滑肌明顯萎縮、細胞排列紊亂，彈性纖維層結構不清；肺臟組織HE染色在小支氣管周圍肺泡間質間可見大量炎癥細胞浸潤、淋巴濾泡形成；腎臟組織HE染色可見腎小球周圍小動脈擴張； 4) PNE組雌性子代大鼠血清IGFBP-3水平比正常對照組顯著降低（P＜0.05）,但是雄性子代大鼠血清IGFBP-3水平與正常對照組無顯著差異（P＞0.05）；此外，PNE組子代大鼠血清IGF-1、IGF-2、IGFBP-1和IGFBP-2水平均與正常對照組無顯著差異（均P＞0.05）； 5)在腎臟組織，正常對照組雄性子代IGF-1、IGF-1R、IGF-2、IGFBP-1、IGFBP-2和IGFBP-3均呈較強表達（+++），而雌性子代則呈弱表達（±～+），PNE組雄性子代（+～++）較正常對照組表達下調，而雌性子代（+～++）則較正常對照組表達上調。在肝臟組織，正常對照組子代IGF-1、IGF-1R、IGF-2、IGFBP-1、IGFBP-2和IGFBP-3均呈弱表達（±～+），而PNE組子代（+～++）表達上調；在肺臟組織， PNE組子代IGF-1、IGF-1R、IGF-2、IGFBP-1、IGFBP-2和IGFBP-3于肺泡間質小動脈周圍細胞胞漿有少量表達（±），而正常對照組未見表達；在胰腺、心臟以及胸主動脈等臟器組織，PNE組與正常對照組均未見表達。 結論 1) PNE可影響5月齡子代大鼠腸系膜動脈內皮依賴/非依賴性血管舒張功能，該效應存在性別差異，提示PNE所致血管內皮功能損傷始于中型肌性動脈，可持續(xù)作用至成年期，且以雄性子代血管內皮功能損傷為特征； 2) PNE可導致5月齡子代大鼠胸主動脈血管內膜及中膜病理結構損害，提示PNE不但可引起血管功能損傷還可導致血管結構的病理改變；此外，還可導致肺臟小支氣管周圍肺泡間質間淋巴濾泡形成、炎癥細胞浸潤； 3) PNE可下調5月齡雌性子代大鼠血清IGFBP-3水平，并導致子代大鼠IGFs及IGFBPs組織特異性表達異常，，其中腎臟的表達水平存在性別差異，PNE對子代IGFs軸的調控可能參與介導PNE誘導的血管內皮功能損傷。
[Abstract]:Background Tobacco exposure is associated with cardiovascular disease , nicotine is the most important pathogenic component in tobacco . In the early stage of life development , the factors such as maternal and other factors can form marks on the embryonic stage . It is not clear that the vascular endothelial function injury and insulin - like growth factors ( IGFs ) axis are involved in the development of cardiovascular disease .

Objective To investigate the effects of prenatal nicotine exposure ( PNE ) on vascular endothelial function and IGFs axis in offspring rats and their potential gender - dependent differences .

Methods 20 SD rats were randomly divided into two groups : PNE group and normal control group , which were implanted subcutaneously with osmotic micro - pump ( 2ML4 type ) , in which PNE group osmotic micro - pump carries nicotine ( 8 mg / kg / day ) , normal control group osmotic micro - pump carries nicotine ( 8 mg / kg / day ) .
Blood samples were collected , and serum IGF - 1 , IGF - 2 , IGFBP3 were measured by ELISA - linked immunosorbent assay ( ELISA ) .
The tissue - specific expression level of IGF - 1 , IGF - 1R , IGF - 2 , IGFBP3 , IGFBP3 and IGF - 1 , IGF - 1R , IGF - 2 , IGFBP3 were detected by HE staining and immunohistochemical staining .

Results

1 ) There was no significant difference between the endothelium - dependent / non - dependent vasodilatation percentage of thoracic aorta and PNE group and normal control group ( P > 0.05 ) .


2 ) The endothelium - dependent / non - dependent vasodilatation percentage of mesenteric artery was significantly lower in PNE group than in normal control group ( P & lt ; 0.05 ) , while the female offspring was significantly higher than that of normal control group ( P & lt ; 0.05 ) .


3 ) HE staining of the thoracic aorta in the offspring rats showed that the lumen was not uneven , the vacuolar degeneration of the endothelial cells , the loss of endothelium , the thickening of the intima , the obvious atrophy of the smooth muscle of the medial membrane , the disorder of the cell arrangement , the structure of the elastic fibrous layer were not clear ;
HE staining of the lung tissue showed a large amount of inflammatory cell infiltration and lymphoid follicles formation between the alveolar spaces around the small bronchus .
The renal tissue HE staining showed the expansion of arterioles around the glomerulus ;


4 ) There was no significant difference ( P < 0 . 05 ) between the levels of serum - 3 - 3 in the serum of the female offspring of the PNE group ( P < 0 . 05 ) , but there was no significant difference between the levels of serum - 3 - 3 and the normal control group ( P > 0 . 05 ) .
In addition , the levels of serum IGF - 1 , IGF - 2 , IGFBP3 and IGF - 2 in the offspring of PNE group were not significantly different from those in the normal control group ( P > 0.05 ) .


In the normal control group , the expression of IGF - 1 , IGF - 1R , IGF - 2 , IGFBP3 , IGFBP3 and IGF - 1R , IGF - 2 , IGFBP3 and IGF - 1 , IGF - 1R , IGF - 2 , IGFBP3 and IGF - 1 , IGF - 1R , IGF - 2 , IGFBP3 and IGF - 1 , IGF - 1R , IGF - 2 , IGFBP3 , IGFBP3 , IGFBP3 and IGF - 1 , IGF - 1R , IGF - 2 , IGFBP3 , IGFBP3 and IGF - 1 , IGF - 1R , IGF - 2 , IGFBP3 , IGFBP3 , IGFBP3 and IGF - 1 , IGF - 1R , IGF - 2 , IGFBP3 , IGFBP3 and IGF - 1 , IGF - 1R , IGF - 2 , IGFBP3 , IGFBP3 and IGF - 1 , IGF - 1R , IGF - 2 , IGFBP3 , IGFBP3 and IGF - 1 , IGF - 1R , IGF - 2 , IGFBP3 , IGFBP3 and IGF - 1 , IGF - 1R , IGF - 2 , IGFBP3 , IGFBP3 and IGF - 1 , IGF - 1R , IGF - 2 , IGFBP3 , IGFBP3 and IGF - 1 , IGF - 1R , IGF - 2 , IGFBP3 , IGFBP3 and IGF - 1 , IGF - 1R , IGF - 2 , IGFBP3 , IGFBP3 and IGF - 1 , IGF - 1R , IGF - 2 , IGFBP3 , IGFBP3 and IGF - 1 , IGF - 1R , IGF - 2 , IGFBP3 , IGFBP3 and IGF - 1 , IGF - 1R , IGF - 2 , IGFBP3 , IGFBP3 and IGF - 1 , IGF - 1R , IGF - 2 , IGFBP3 , IGFBP3 and IGF - 1 , IGF - 1R , IGF - 2 , IGFBP3 , IGFBP3 and IGF - 1 , IGF - 1R , IGF - 2 , IGFBP3 , IGFBP3 and IGF - 1 , IGF - 1R , IGF - 2 , IGFBP3 , IGFBP3 and IGF - 1 , IGF - 1R , IGF - 2 ,
There was a small expression of IGF - 1 , IGF - 1R , IGF - 2 , IGFBP3 in the pulmonary tissue , PNE group , IGF - 1 , IGF - 1R , IGF - 2 , IGFBP3 and IGFBP3 .
In the pancreas , heart and thoracic aorta , the PNE group and the normal control group were not expressed .

Conclusion

1 ) PNE can affect the endothelium - dependent / non - dependent vasodilatation function of mesenteric artery in 5 - month - old offspring rats , and the effect is gender difference , suggesting that the damage of vascular endothelial function caused by PNE starts from the medium - sized muscular artery , which can be continuously applied to adulthood , and is characterized by the injury of the endothelial function of the vascular endothelium in the male offspring ;


2 ) PNE can lead to the damage of vascular intima and pathological structure of thoracic aorta in 5 - month - old rats , suggesting that PNE not only can cause vascular function injury but also can lead to pathological changes of vascular structure ;
In addition , it can also lead to the formation of lymph follicles and infiltration of inflammatory cells in the interstitial interstitial spaces around the lungs of the lungs .


3 ) PNE could down - regulate the levels of serum levels of IGFs and IGFBPs in the offspring of 5 - month - old female rats , and lead to abnormal expression of IGFs and IGFBPs in offspring rats , in which the expression level of PNE is gender difference , and the regulation of PNE on children ' s IGFs may be involved in mediating the vascular endothelial function injury induced by PNE .
【學位授予單位】：福建醫(yī)科大學
【學位級別】：碩士
【學位授予年份】：2013
【分類號】：R114

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相關期刊論文 前2條

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2 李彥清,邵龍江,李森,鄧澤沛,祝誠;大鼠陰栓的實驗觀察和孕鼠模型鑒定方法的比較[J];中國實驗動物學雜志;2002年01期

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