孕期LPS刺激對子代6周齡大鼠血管結構的影響
發(fā)布時間:2018-07-06 21:37
本文選題:孕期炎癥刺激 + 血管結構。 參考:《中國藥理學通報》2017年05期
【摘要】:目的研究孕期炎癥刺激劑脂多糖(lipopolysaccharides,LPS)刺激對子代大鼠6周齡時血管結構的影響。方法 12只Sprague dawley(SD)孕鼠隨機分為3組:對照組(control,Con)、LPS刺激組、LPS刺激加二硫代氨基四氫呋喃(pyrrolidinedithiocarbamate,PDTC)干預組(L+P),分別在孕8~14 d腹腔注射生理鹽水、LPS(0.79 mg·kg~(-1))或LPS加PDTC(100 mg·kg~(-1)),LPS于孕d 8、10、12給藥;生理鹽水及PDTC于d 8~14每天給藥。子代出生6周測體質量;透射電鏡觀察血管超微結構;實時熒光定量PCR檢測仔鼠胸主動脈連接蛋白(connexin,Cx)Cx37、Cx40、Cx43、Cx45的mRNA表達水平;Western blot和免疫熒光檢測仔鼠胸主動脈Cx37、Cx40、Cx43、Cx45的蛋白表達水平。結果與Con組相比,LPS組子代大鼠在6周時♂♀體質量均明顯增加(P0.01);L+P組♂鼠明顯低于LPS組(P0.05),而♀鼠差異無顯著性。LPS組內皮受損,內皮細胞間可見明顯縫隙連接(gap junction,GJ),相對于Con組較長且多見;L+P組內皮損傷程度較LPS組稍有改善。LPS組Cx43 mRNA及蛋白表達均明顯低于Con組(P0.05),L+P組則明顯高于LPS組(P0.05);Cx37、Cx40和Cx45各組間mRNA及蛋白表達差異無統(tǒng)計學意義。LPS組Cx43熒光強度及熒光點數(shù)明顯比Con組降低,而L+P組明顯比LPS組高,各組間Cx37、Cx40和Cx45熒光強度和熒光點數(shù)并無明顯差異。結論孕期LPS刺激可致子代大鼠在6周齡時出現(xiàn)血管結構損傷,這種損傷可能持續(xù)于新生兒期,并與其成年發(fā)生高血壓密切相關。
[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.
【作者單位】: 第三軍醫(yī)大學藥學系藥物研究所;大理大學基礎醫(yī)學院病理學教研室;
【基金】:國家自然科學基金資助項目(No 81373420,81573440,81273507,81473210)
【分類號】:R714.2
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本文編號:2104160
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