牙周炎孕鼠影响成年子代脂肪细胞对胰岛素敏感性的研究
Periodontal disease in pregnancy rats induced insulin resistance in adipose cell of adult offspring
目的 探讨牙周炎孕鼠与子代出生低体重的关系以及是否会引起成年子代脂肪细胞产生胰岛素抵抗。 方法 将12只雌性成年Wistar大鼠分成实验性牙周炎组（PD）和对照组（CN），每组各6只。牙周炎组造模7 d后，两组大鼠均与健康雄鼠交配。待孕鼠产后，将雄性子代分为牙周炎子代组（PDO）和对照子代组（CNO），每组18只，分别测新生鼠出生体重和每周体重直至11周。11周后，将所有两组鼠麻醉，分组采血、处死，测血糖、血胰岛素、脂联素、TNF-α、脂肪细胞蛋白激酶B（Akt）丝氨酸磷酸化水平及葡萄糖转运蛋白4（Glut4）的表达水平。 结果 两组新生鼠的出生体重、每周体重和血糖浓度没有统计学差异（P>0.05），PDO组的血胰岛素、脂联素和TNF-α均高于CNO组（P<0.05），胰岛素诱导两组蛋白激酶B丝氨酸磷酸化（p-Akt）水平增加（P<0.05），且胰岛素刺激后PDO组p-Akt水平更低（P<0.05），PDO组Glut4在质膜的表达水平低于CNO组（P<0.05）。 结论 虽然牙周炎孕鼠的子代出生并无低体重，但是可以引起成年子代脂肪细胞产生胰岛素抵抗。
Objective To explore the relationship between maternal periodontal disease and PLBW and whether the offspring of rats with periodontal disease develop insulin resistance in adulthood. Methods 12 female Wistar rats were divided into Periodontal disease (PD) and control (CN) groups, with 6 rats in each group. The rats in two groups were mated at the seventh day after induction of Periodontal disease. After delivery, male offspring were divided into Periodontal disease offspring (PDO) and control offspring (CNO), with 18 rats each group. Weight of the newborns was measured from birth to eleventh week. 11 weeks later, all offspring rats were euthanized and the glycemia, insulinemia, adiponectin content, level of TNF-α, Akt serine phosphorylation levels and Glut4 content in the adipose tissue were measured. Results Weight of birth, weekly body weight and glucose content had no difference between CNO and PDO groups (P>0.05). However, the concentrations of insulin, adiponectin and TNF-α were increased in PDO group compared to CNO group. Akt serine phosphorylation levels increased in both groups after insulin stimulation (P<0.05), but PDO group increased less than CNO group(P<0.05). Expression level of Glut4 in the adipose tissue decreased in PDO group compared to CNO group(P<0.05). Conclusion There is no relationship between maternal periodontal disease and PLBW, but periodontal disease during pregnancy can induce insulin resistance in adipose cell of adult offspring.
牙周炎 / 胰岛素抵抗 / 2型糖尿病 / 葡萄糖转运蛋白4
/ Periodontal disease / Insulin resistance / Type 2 diabetes / Glut4
[1] Sert T, K?rz?o?lu FY, Fento?lu O, et al. Serum placental growth factor, vascular endothelial growth factor, soluble vascular endothelial growth factor receptor-1 and -2 levels in periodontal disease, and adverse pregnancy outcomes[J]. J Periodontol, 2011, 82(12): 1735-1748.
[2] Detzen L, Chen SCY, Cheng B, et al. Increased levels of soluble CD163 in periodontitis patients[J]. J Clin Periodontol, 2017, 44(6): 585-590.
[3] Colombo NH, Shirakashi DJ, Chiba FY, et al. Periodontal disease decreases insulin sensitivity and insulin signaling[J]. J Periodontol, 2012, 83(7): 864-870.
[4] Ercan E, Eratalay K, Deren O, et al. Evaluation of periodontal pathogens in amniotic fluid and the role of periodontal disease in pre-term birth and low birth weight[J]. Acta Odontol Scand, 2013, 71(3-4):553-559.
[5] Guimarães AN, Silva-Mato A, Siqueira FM, et al. Very low and low birth weight associated with maternal periodontitis[J]. J Clin Periodontol, 2012, 39(11): 1024-1031.
[6]Haerian-Ardakani A, Eslami Z, Rashidi-Meibodi F, et al. Relationship between maternal periodontal disease and low birth weight babies[J]. Iran J Reprod Med, 2013, 11(8):625-630.
[7] Kim CS, Park JS, Park J, et al. The relation between birth weight and insulin resistance in Korean adolescents[J]. Yonsei Med J, 2006, 47(1):85-92.
[8] Ryu JI, Oh K, Yang H, et al. Health behaviors, periodontal conditions, and periodontal pathogens in spontaneous preterm birth: A case-control study in Korea[J]. J Periodontol, 2010, 81(6):855-863.
[9] Shirakashi DJ，Leal RP，Colombo NH，et al. Maternal periodontal disease in rats decreases insulin sensitivity and insulin signaling in adult offspring[J]. J Periodontol, 2013, 84(3):407-414．
[10]Welsh GI, Hers I, Berwick DC, et al. Role of protein kinase B in insulin-regulated glucose uptake[J], Biochem Soc Trans, 2005, 33(Pt 2):346-349.
[11]Mannem s, Chava VK. The relationship between maternal periodontitis and preterm low birth weight: a case-control study[J]. Contemp Clin Dent, 2011, 2(2): 88-93.
[12]谭清梅, 杨诚, 廖坚文, 等. 二甲双胍通过AMPK信号通路对小鼠骨关节炎保护作用的研究[J]. 中国临床解剖学杂志, 2017, 35(4): 413-418.
[13]Cianfarani S, Germani D, Branca F. Low birthweight and adult insulin resistance: the “catch-up growth” hypothesis[J]. Arch Dis Child Fetal Neonatal Ed, 1999, 81(1): F71-F73.
[14]Xynogala I, Pepelassi E, Perrea D, et al. Adiponectin and interleukin-6 levels in insulin-treated diabetic rats with experimental periodontitis[J]. Braz Oral Res, 2012, 26(1): 71-76.
[15]Lin D, Smith MA, Champagne C, et al. Porphyromonas gingivalis infection during pregnancy increases maternal tumor necrosis factor alpha, suppresses maternal interleukin-10, and enhances fetal growth restriction and resorption in mice[J]. Infect Immun, 2003, 71(9): 5156-5162.
[16]Sert T, K?rz?o?lu FY, Fento?lu O, et al. Serum placental growth factor,vascular endothelial growth factor, soluble vascular endothelial growth factor receptor-1 and -2 levels in periodontal disease, and adverse pregnancy outcomes[J]. J Periodontol, 2011, 82(12): 1735-1748.
[17]Plomgaard P, Bouzakri K, Krogh-Madsen R, et al. Tumor necrosis factor-alpha induces skeletal muscle insulin resistance in healthy human subjects via inhibition of Akt substrate 160 phosphorylation[J], Diabetes, 2005, 54 (10): 2939-2945.
[18] Huang S, Czech MP. The GLUT4 glucose transporter[J], Cell Metab, 2007, 5(4): 237-252.
[19]Rowland AF, Fazakerley DJ, James DE. Mapping insulin/GLUT4 circuitry[J]. Traffic, 2011, 12(6):672-681.
[20]Berglund ED, Li CY, Ayala JE, et al. Regulation of endogenous glucose production in glucose transporter 4 over-expressing mice[J], PLoS One, 2012, 7(12): e52355.
[21]Carvalho E, Kotani K, Peroni OD, et al. Adipose-specific overexpression of GLUT4 reverses insulin resistance and diabetes in mice lacking GLUT4 selectively in muscle[J], Am J Physiol Endocrinol Metab, 2005, 289(4): E551-E561.
京ICP备08002354号-3/
| 〈 |
|
〉 |
