DEHP低劑量慢性暴露對(duì)雌性大鼠糖代謝的影響
發(fā)布時(shí)間:2018-07-06 19:49
本文選題:鄰苯二甲酸二(-乙基己基)酯 + 慢性; 參考:《環(huán)境與職業(yè)醫(yī)學(xué)》2017年08期
【摘要】:[目的]觀察鄰苯二甲酸二(2-乙基己基)酯(DEHP)低劑量慢性暴露對(duì)雌性大鼠糖代謝的影響。[方法]將24只SPF級(jí)雌性SD大鼠隨機(jī)分為4組,分別為0、3、30、300 mg/kg(以體重計(jì),后同)DEHP染毒組,每組6只,采用喂飼的方式連續(xù)染毒46周,定期測(cè)量大鼠空腹血糖,并記錄體重變化。于末次染毒24 h后,稱量大鼠體重,分別進(jìn)行口服葡萄糖耐量試驗(yàn)(OGTT)、胰島素耐量實(shí)驗(yàn)(ITT),計(jì)算曲線下面積(AUC);隨后水合氯醛麻醉,心尖取血處死,取肝臟、胰腺、生殖器周?chē)咨、腓腸肌稱重,并保存于10%(體積分?jǐn)?shù))中性福爾馬林中固定,用于組織病理形態(tài)觀察(腓腸肌除外)。[結(jié)果]DEHP染毒期間,各組大鼠均未出現(xiàn)明顯毒作用表現(xiàn)。與0 mg/kg組比較:(1)各實(shí)驗(yàn)組大鼠體重差異均無(wú)統(tǒng)計(jì)學(xué)意義(P0.05)。(2)300 mg/kg組大鼠肝臟臟器系數(shù)升高(P0.05),其余劑量組均無(wú)統(tǒng)計(jì)學(xué)差異(P0.05);各實(shí)驗(yàn)組胰腺、生殖器周?chē)咨、腓腸肌臟器系數(shù)差異均無(wú)統(tǒng)計(jì)學(xué)意義(P0.05)。(3)DEHP暴露18周后,300 mg/kg大鼠空腹血糖升高(P0.05),其他時(shí)點(diǎn)各組差異均無(wú)統(tǒng)計(jì)學(xué)意義(P0.05);各組HOMA-IR、ISI、血清胰島素水平差異均無(wú)統(tǒng)計(jì)學(xué)意義(P0.05)。(4)OGTT結(jié)果顯示,雌性大鼠300 mg/kg組服糖后血糖濃度峰值出現(xiàn)早[15 min出現(xiàn)峰值(P=0.004)],而服糖后60、120 min時(shí)血糖濃度明顯下降(P=0.038,P=0.039),且服糖后120 min血糖濃度低于空腹水平,血糖AUC降低(P=0.040);ITT實(shí)驗(yàn)結(jié)果顯示,30 mg/kg組血糖值在15 min時(shí)明顯低于0 mg/kg組(P=0.029),300 mg/kg組血糖值下降較為明顯,在60、120 min時(shí)血糖值下降超過(guò)空腹血糖的50%(P=0.017,P=0.038),且恢復(fù)至空腹血糖值緩慢,300 mg/kg組血糖AUC降低(P=0.028)。肝臟病理形態(tài)結(jié)果顯示:各DEHP染毒組大鼠肝細(xì)胞出現(xiàn)不同程度增大、水腫,間質(zhì)疏松,可見(jiàn)不同程度膽管周?chē)。胰腺病理形態(tài)結(jié)果顯示:各DEHP染毒組大鼠胰島面積減小、細(xì)胞數(shù)量減少。生殖器周?chē)咨静±硇螒B(tài)結(jié)果顯示各DEHP染毒組大鼠脂肪細(xì)胞不同程度縮小、大小不一,細(xì)胞排列不整齊。[結(jié)論]DEHP低劑量慢性暴露可能導(dǎo)致雌性大鼠發(fā)生胰島素抵抗。
[Abstract]:[objective] to observe the effect of low dose chronic exposure of bis (2 ethylhexyl) phthalate (DEHP) on glucose metabolism in female rats. [methods] Twenty-four SPF female Sprague-Dawley rats were randomly divided into 4 groups. The rats in each group were treated with DEHP for 30 300 mg/kg, 6 rats in each group were fed continuously for 46 weeks. Fasting blood glucose was measured regularly and the changes of body weight were recorded. 24 hours after the last exposure, the rats were weighed by oral glucose tolerance test (OGTT), insulin tolerance test (ITT), area under curve (AUC), followed by chloral hydrate anesthesia. White fat around genitalia, gastrocnemius weighing, and fixed in 10% (volume fraction) neutral formalin for histopathological observation (except gastrocnemius). [results] during the period of DEHP exposure, no obvious toxic effect was found in all groups. Compared with 0 mg/kg group: (1) there was no significant difference in body weight of each experimental group (P0.05). (2). The liver organ coefficient of 300 mg/kg group was increased (P0.05), and the other dose groups had no statistical difference (P0.05); the pancreas of each experimental group, white fat around genitalia, white fat around genitalia, There was no significant difference in the organ coefficient of gastrocnemius muscle (P0.05) (P0.05). The fasting blood glucose of rats exposed to DEHP for 18 weeks was increased (P0.05), but there was no significant difference at other time points (P0.05). There was no significant difference in HOMA-IRISI, serum insulin level (P0.05). (4). In female rats, the peak of glucose concentration appeared early after taking glucose for 60120 min (P0. 004), but decreased significantly at 60120 min after taking glucose (P0. 038, P0. 039), and the blood glucose concentration of 120 min was lower than that of fasting after taking glucose. The results of ITT test showed that the blood glucose level of 30 mg/kg group was significantly lower than that of 0 mg/kg group (P0. 029) 30 mg/kg group at 15 min. At 60120 min, the blood glucose decreased by more than 50% of the fasting blood glucose (P0. 017, P0. 038), and recovered to the fasting blood glucose level slowly to the 300 mg/kg group, the blood glucose AUC decreased (P0. 028). The pathological morphology of the liver showed that the liver cells were increased, edema, interstitial looseness and pericholangitis were observed in different DEHP groups. The pancreatic histopathological results showed that the islet area and the number of cells decreased in each DEHP group. The histopathological results of white fat around genitals showed that adipocytes of rats exposed to DEHP decreased to different degrees, size varied, and cells were not arranged neatly. [conclusion] low dose chronic exposure to DEHP may lead to insulin resistance in female rats.
【作者單位】: 寧夏醫(yī)科大學(xué)生育力保持教育部重點(diǎn)實(shí)驗(yàn)室;寧夏醫(yī)科大學(xué)公共衛(wèi)生與管理學(xué)院勞動(dòng)衛(wèi)生與環(huán)境衛(wèi)生學(xué)系;寧夏醫(yī)科大學(xué)總醫(yī)院腫瘤醫(yī)院病理科;
【基金】:寧夏醫(yī)科大學(xué)2014年中央與地方共建優(yōu)秀創(chuàng)新團(tuán)隊(duì)項(xiàng)目(編號(hào):30100402)
【分類號(hào)】:R114
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