中华内科杂志
中華內科雜誌
중화내과잡지
CHINESE JOURNAL OF INTERNAL MEDICINE
2014年
6期
482-486
,共5页
李燕%陈璐璐%胡祥%余珊%郑涓%黎慧清%曾天舒%夏文芳%张皎月
李燕%陳璐璐%鬍祥%餘珊%鄭涓%黎慧清%曾天舒%夏文芳%張皎月
리연%진로로%호상%여산%정연%려혜청%증천서%하문방%장교월
胰岛素抗药性%追赶生长%NALP3炎性体
胰島素抗藥性%追趕生長%NALP3炎性體
이도소항약성%추간생장%NALP3염성체
Insulin resistance%Catch-up growth%NALP3 inflammasome
目的 观察追赶生长(CUG)对内脏脂肪NOD样受体蛋白3(NALP3)炎性体通路的影响,探讨追赶生长大鼠胰岛素抵抗的形成机制.方法 SD大鼠分为普通饮食组(NC)和追赶生长组(CUG),实验4、6、8周检测腹部脂肪含量(AFM％)、高胰岛素-正糖钳夹试验中葡萄糖输注率(GIR60-120)以及肾周脂肪NALP3炎性体、效应分子半胱天冬酶-1(caspase1)和IL-1β表达.结果 限食4周末,与NC组比较,CUG组AFM％明显下降[(11.54±1.81)％比(7.72±1.47)％,P＜0.05],肾周脂肪NALP3炎性体(0.47±0.03比0.28 ±0.04,P＜0.01)、caspase1(p10)(0.30±0.02比0.20 ±0.03,P＜0.01)和IL-1β (p17)(0.52 ±0.04比0.37 ±0.04,P＜0.05)表达也显著降低,而GIR60-120略升高[(23.47±0.89) mg·min-1·kg-1比(25.34±1.16) mg·min-1·kg-1,P＞0.05].恢复饮食后,CUG组AFM％、NALP3炎性体、caspase1(p10)和IL-1β (p17)表达逐渐增加,GIR60-120相应下降;至恢复饮食4周时,CUG组AFM％、NALP3炎性体、caspase1 (p10)和IL-13(p17)表达显著高于NC组[分别是(15.16±1.10)％比(12.52 ±0.64)％,P＜0.01;0.65 ±0.05比0.52 ±0.02,P＜0.05;0.54±0.02比0.33±0.03,P＜0.01;0.65 ±0.05比0.55 ±0.04,P＜0.05],而GIR60-120明显低于NC组[(14.27±1.06) mg· min-1·kg-1比(21.45±1.20) mg·min-1·kg-1,P＜0.05].相关分析显示,肾周脂肪NALP3和caspase1 (p10)表达与AFM％正相关(r=0.946,r=0.922,P值均＜0.01),与GIR60-120负相关(r=-0.902,r=-0.944,P值均＜0.01).结论 CUG能显著激活内脏脂肪NALP3炎性体通路,这可能是CUG胰岛素抵抗形成的重要机制.
目的 觀察追趕生長(CUG)對內髒脂肪NOD樣受體蛋白3(NALP3)炎性體通路的影響,探討追趕生長大鼠胰島素牴抗的形成機製.方法 SD大鼠分為普通飲食組(NC)和追趕生長組(CUG),實驗4、6、8週檢測腹部脂肪含量(AFM％)、高胰島素-正糖鉗夾試驗中葡萄糖輸註率(GIR60-120)以及腎週脂肪NALP3炎性體、效應分子半胱天鼕酶-1(caspase1)和IL-1β錶達.結果 限食4週末,與NC組比較,CUG組AFM％明顯下降[(11.54±1.81)％比(7.72±1.47)％,P＜0.05],腎週脂肪NALP3炎性體(0.47±0.03比0.28 ±0.04,P＜0.01)、caspase1(p10)(0.30±0.02比0.20 ±0.03,P＜0.01)和IL-1β (p17)(0.52 ±0.04比0.37 ±0.04,P＜0.05)錶達也顯著降低,而GIR60-120略升高[(23.47±0.89) mg·min-1·kg-1比(25.34±1.16) mg·min-1·kg-1,P＞0.05].恢複飲食後,CUG組AFM％、NALP3炎性體、caspase1(p10)和IL-1β (p17)錶達逐漸增加,GIR60-120相應下降;至恢複飲食4週時,CUG組AFM％、NALP3炎性體、caspase1 (p10)和IL-13(p17)錶達顯著高于NC組[分彆是(15.16±1.10)％比(12.52 ±0.64)％,P＜0.01;0.65 ±0.05比0.52 ±0.02,P＜0.05;0.54±0.02比0.33±0.03,P＜0.01;0.65 ±0.05比0.55 ±0.04,P＜0.05],而GIR60-120明顯低于NC組[(14.27±1.06) mg· min-1·kg-1比(21.45±1.20) mg·min-1·kg-1,P＜0.05].相關分析顯示,腎週脂肪NALP3和caspase1 (p10)錶達與AFM％正相關(r=0.946,r=0.922,P值均＜0.01),與GIR60-120負相關(r=-0.902,r=-0.944,P值均＜0.01).結論 CUG能顯著激活內髒脂肪NALP3炎性體通路,這可能是CUG胰島素牴抗形成的重要機製.
목적 관찰추간생장(CUG)대내장지방NOD양수체단백3(NALP3)염성체통로적영향,탐토추간생장대서이도소저항적형성궤제.방법 SD대서분위보통음식조(NC)화추간생장조(CUG),실험4、6、8주검측복부지방함량(AFM％)、고이도소-정당겸협시험중포도당수주솔(GIR60-120)이급신주지방NALP3염성체、효응분자반광천동매-1(caspase1)화IL-1β표체.결과 한식4주말,여NC조비교,CUG조AFM％명현하강[(11.54±1.81)％비(7.72±1.47)％,P＜0.05],신주지방NALP3염성체(0.47±0.03비0.28 ±0.04,P＜0.01)、caspase1(p10)(0.30±0.02비0.20 ±0.03,P＜0.01)화IL-1β (p17)(0.52 ±0.04비0.37 ±0.04,P＜0.05)표체야현저강저,이GIR60-120략승고[(23.47±0.89) mg·min-1·kg-1비(25.34±1.16) mg·min-1·kg-1,P＞0.05].회복음식후,CUG조AFM％、NALP3염성체、caspase1(p10)화IL-1β (p17)표체축점증가,GIR60-120상응하강;지회복음식4주시,CUG조AFM％、NALP3염성체、caspase1 (p10)화IL-13(p17)표체현저고우NC조[분별시(15.16±1.10)％비(12.52 ±0.64)％,P＜0.01;0.65 ±0.05비0.52 ±0.02,P＜0.05;0.54±0.02비0.33±0.03,P＜0.01;0.65 ±0.05비0.55 ±0.04,P＜0.05],이GIR60-120명현저우NC조[(14.27±1.06) mg· min-1·kg-1비(21.45±1.20) mg·min-1·kg-1,P＜0.05].상관분석현시,신주지방NALP3화caspase1 (p10)표체여AFM％정상관(r=0.946,r=0.922,P치균＜0.01),여GIR60-120부상관(r=-0.902,r=-0.944,P치균＜0.01).결론 CUG능현저격활내장지방NALP3염성체통로,저가능시CUG이도소저항형성적중요궤제.
Objective To investigate the effects of catch-up growth(CUG) on the natch domain,leucine-rich repeat and PVD-containing protein 3 (NALP3) inflammasome pathway in visceral adipose tissue (VAT) and the mechanism of insulin resistance (IR) in CUG.Methods Sprague-Dawley rats were randomly divided into the normal chow (NC) and the catch-up growth group (CUG).General characteristics,glucose infusion rate60-120 (GIR60-120) in hyperinsulinemic-euglycemic clamp and expression of NALP3 inflammasome,caspase1 (p10)and IL-1β (p17) cleavage in VAT were respectively examined on week 4,6 and 8 of the experiment.Results After 4-week food restriction,lower percentage of abdominal fat mass (AFM％) was presented in the CUG group than the NC group [(11.54 ± 1.81)％ vs (7.72 ±1.47) ％,P ＜ 0.05].In the CUG group,decreased expression of NALP3 inflammasome,caspase1 (p10)and IL-1 5 (p17) cleavage in VAT were found (0.47 ± 0.03 vs 0.28 ± 0.04,P ＜ 0.01 ; 0.30 ± 0.02 vs 0.20 ± 0.03,P ＜ 0.01 ; 0.52 ± 0.04 vs 0.37 ± 0.04,P ＜ 0.05 ; respectively),whereas GIR60-120 was slightly improved [(23.47 ±0.89)mg · min-1 · kg-1 vs (25.34 ± 1.16) mg · min-1 · kg-1,P＞0.05].After refeeding,AFM％ and the expression of NALP3 inflammasome,caspase1 (p10) and IL-1β (p17)cleavage in VAT in CUG group were shown to be increased with the time.Concomitant with those changes,GIR60-120 was gradually impaired.On week 4 of refeeding,AFM％ and the expression of NALP3 inflammasome,caspase1 (p10)and IL-1β(p17) cleavage in VAT were significantly increased in the CUGgroup compared with the NC group [(12.52 ±0.64)％ vs (15.16 ± 1.10)％,P ＜0.01 ; 0.52 ±0.02 vs 0.65±0.05,P＜0.05;0.33±0.03 vs0.54±0.02,P＜0.01; 0.55±0.04 vs0.65±0.05,P＜0.05;respectively],while GIR60-120 was significantly attenuated [(21.45 ± 1.20)mg· min-1 · kg-1 vs (14.27 ± 1.06) mg · min-1 · kg-1,P ＜ 0.05].Correlation analysis showed that the expression of NALP3 and caspase1 (p10) in VAT were positively correlated with AFM％ (r =0.946,P ＜ 0.01 ; r =0.922,P ＜0.01),while negatively correlated with GIR60-120 (r =-0.902,P ＜ 0.01 ; r =-0.944,P ＜ 0.01).Conclusion NALP3 inflammasome pathway in VAT is notably activated during CUG,which may contribute to the etiology of IR in CUG.
