孕期LPS刺激对子代6周龄大鼠血管结构的影响

发布时间：2018-07-06 21:37

  本文选题：孕期炎症刺激 + 血管结构　； 参考：《中国药理学通报》2017年05期

【摘要】：目的研究孕期炎症刺激剂脂多糖(lipopolysaccharides,LPS)刺激对子代大鼠6周龄时血管结构的影响。方法 12只Sprague dawley(SD)孕鼠随机分为3组:对照组(control,Con)、LPS刺激组、LPS刺激加二硫代氨基四氢呋喃(pyrrolidinedithiocarbamate,PDTC)干预组(L+P),分别在孕8~14 d腹腔注射生理盐水、LPS(0.79 mg·kg~(-1))或LPS加PDTC(100 mg·kg~(-1)),LPS于孕d 8、10、12给药;生理盐水及PDTC于d 8~14每天给药。子代出生6周测体质量;透射电镜观察血管超微结构;实时荧光定量PCR检测仔鼠胸主动脉连接蛋白(connexin,Cx)Cx37、Cx40、Cx43、Cx45的mRNA表达水平;Western blot和免疫荧光检测仔鼠胸主动脉Cx37、Cx40、Cx43、Cx45的蛋白表达水平。结果与Con组相比,LPS组子代大鼠在6周时♂♀体质量均明显增加(P0.01);L+P组♂鼠明显低于LPS组(P0.05),而♀鼠差异无显著性。LPS组内皮受损,内皮细胞间可见明显缝隙连接(gap junction,GJ),相对于Con组较长且多见;L+P组内皮损伤程度较LPS组稍有改善。LPS组Cx43 mRNA及蛋白表达均明显低于Con组(P0.05),L+P组则明显高于LPS组(P0.05);Cx37、Cx40和Cx45各组间mRNA及蛋白表达差异无统计学意义。LPS组Cx43荧光强度及荧光点数明显比Con组降低,而L+P组明显比LPS组高,各组间Cx37、Cx40和Cx45荧光强度和荧光点数并无明显差异。结论孕期LPS刺激可致子代大鼠在6周龄时出现血管结构损伤,这种损伤可能持续于新生儿期,并与其成年发生高血压密切相关。
[Abstract]:Objective to study the effects of lipopolysaccharide polysaccharide (LPS) on vascular structure in 6 weeks old rats. Methods Twelve pregnant rats with Sprague dawley (SD) were randomly divided into three groups: control group (control group) and control group (LPS-stimulated group) treated with LPS plus pyrrolidine dithiocarbamate (LP). LPS was injected intraperitoneally on day 814 of gestation with normal saline LPS (0.79 mg kg-1) or LPS plus PDTC (100mg kg-1) on gestational day 810. Normal saline and PDTC were given daily on d 814. Body mass was measured at 6 weeks of birth, ultrastructure of blood vessels was observed by transmission electron microscope (TEM), expression of connexin Cx (Cx37) Cx40 Cx43 Cx45 mRNA was detected by real-time fluorescence quantitative PCR. Western blot and immunofluorescence were used to detect the protein expression of Cx37 Cx40Cx43 Cx45 in thoracic aorta. Results compared with the Con group, the body weight of lipopolysaccharide (LPS) group was significantly increased (P0.01) than that of LPS group (P0.05), but the endothelium of lipopolysaccharide group had no significant difference. There was obvious gap junctional junction GJ between endothelial cells. Compared with Con group, the injury degree of endothelial cells in LP group was slightly improved. The expression of Cx43 mRNA and protein in LPS group was significantly lower than that in Con group (P0.05). The expression of Cx43 mRNA and protein in LPS group was significantly higher than that in LPS group (P0.05) Cx37 Cx40 and Cx45. There was no significant difference in mRNA and protein expression among groups. The fluorescence intensity and number of Cx43 in LPS group were significantly lower than those in Con group. However, the fluorescence intensity and number of Cx37 Cx40 and Cx45 in LP group were significantly higher than that in LPS group. Conclusion LPS stimulation during pregnancy can induce vascular structure damage in offspring at the age of 6 weeks, which may persist in the neonatal stage and is closely related to adult hypertension.
【作者单位】： 第三军医大学药学系药物研究所;大理大学基础医学院病理学教研室;
【基金】：国家自然科学基金资助项目(No 81373420,81573440,81273507,81473210)
【分类号】：R714.2
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本文编号：2104160