Shanyu Zhao1, Ya Liu1, Xiaohui Li2. 1. Department of Pharmaceutics, College of Pharmacy, Third Military Medical University, Chongqing 400038, China. 2. Department of Pharmaceutics, College of Pharmacy, Third Military Medical University, Chongqing 400038, China. Email: lpsh008@aliyun.com.
Abstract
OBJECTIVE: To explore the role of prenatal exposure to lipopolysaccharides (LPS) on aortic morphology in the neonatal offspring rats. METHODS: Twelve pregnant rats were randomly divided into three groups: control group, LPS group, and PDTC (pyrrolidinedithiocarbamate, LPS+PDTC) group. The rats were intraperitoneally administered vehicle, LPS (0.79 mg/kg) , or LPS plus PDTC (100 mg/kg) , respectively. LPS was given on the 8th, 10th and 12th days, whereas vehicle and PDTC were given daily from the 8th to the 14th day during gestation. Histopathological alteration of the thoracic aorta was observed by hematoxylin-eosin staining and transmission electron microscopy, thoracic aortic mRNA and protein expression of connexin (Cx) molecules including Cx37, Cx40, Cx43 and Cx45 in offspring was detected by Real Time PCR and confocal laser-scanning microscope, respectively, offspring body weight was measure at day 1 and week 1. RESULTS: Body weight at 1 day and 1 week-old offspring was significantly lower in LPS group than in control group (P < 0.01), which were significantly higher in PDTC group compared to LPS group (P < 0.01): [1 day: control group (7.425 ± 0.146) g, LPS group (6.742 ± 0.128) g, PDTC group (7.137 ± 0.141) g; 1 week: control group (20.173 ± 3.982) g, LPS group (13.264 ± 2.581) g, PDTC group (17.863 ± 3.412) g]. In 1 week-old offspring of LPS group, the thoracic aortas exhibited lesions, including impaired endothelial cells, thickening and fibrous changes of intimae, and migration and proliferation of vascular smooth muscle cells; the number of gap junction was decreased versus control group and pathological changes were similar between PDTC group and LPS group. Cx43 protein expression in LPS group was obviously lower than in control group and which could be partly reversed in PDTC group. Expression of Cx43 mRNA was significantly lower in 1 day and 1 week offspring of LPS group compared to control group (P < 0.05), which could be reversed in PDTC group (P < 0.05) (1 day: control group 1.530 ± 0.296, LPS group 1.226 ± 0.209, PDTC group 1.619 ± 0.324; 1 week: control group 9.357 ± 1.917, LPS group 7.204 ± 1.165, PDTC group 9.271 ± 1.514). CONCLUSION: Our results indicate that maternal LPS exposure during pregnancy leads to vascular changes in neonatal offspring which might increase the susceptibility to adult hypertension.
OBJECTIVE: To explore the role of prenatal exposure to lipopolysaccharides (LPS) on aortic morphology in the neonatal offspring rats. METHODS: Twelve pregnant rats were randomly divided into three groups: control group, LPS group, and PDTC (pyrrolidinedithiocarbamate, LPS+PDTC) group. The rats were intraperitoneally administered vehicle, LPS (0.79 mg/kg) , or LPS plus PDTC (100 mg/kg) , respectively. LPS was given on the 8th, 10th and 12th days, whereas vehicle and PDTC were given daily from the 8th to the 14th day during gestation. Histopathological alteration of the thoracic aorta was observed by hematoxylin-eosin staining and transmission electron microscopy, thoracic aortic mRNA and protein expression of connexin (Cx) molecules including Cx37, Cx40, Cx43 and Cx45 in offspring was detected by Real Time PCR and confocal laser-scanning microscope, respectively, offspring body weight was measure at day 1 and week 1. RESULTS: Body weight at 1 day and 1 week-old offspring was significantly lower in LPS group than in control group (P < 0.01), which were significantly higher in PDTC group compared to LPS group (P < 0.01): [1 day: control group (7.425 ± 0.146) g, LPS group (6.742 ± 0.128) g, PDTC group (7.137 ± 0.141) g; 1 week: control group (20.173 ± 3.982) g, LPS group (13.264 ± 2.581) g, PDTC group (17.863 ± 3.412) g]. In 1 week-old offspring of LPS group, the thoracic aortas exhibited lesions, including impaired endothelial cells, thickening and fibrous changes of intimae, and migration and proliferation of vascular smooth muscle cells; the number of gap junction was decreased versus control group and pathological changes were similar between PDTC group and LPS group. Cx43 protein expression in LPS group was obviously lower than in control group and which could be partly reversed in PDTC group. Expression of Cx43 mRNA was significantly lower in 1 day and 1 week offspring of LPS group compared to control group (P < 0.05), which could be reversed in PDTC group (P < 0.05) (1 day: control group 1.530 ± 0.296, LPS group 1.226 ± 0.209, PDTC group 1.619 ± 0.324; 1 week: control group 9.357 ± 1.917, LPS group 7.204 ± 1.165, PDTC group 9.271 ± 1.514). CONCLUSION: Our results indicate that maternal LPS exposure during pregnancy leads to vascular changes in neonatal offspring which might increase the susceptibility to adult hypertension.