中华糖尿病杂志
中華糖尿病雜誌
중화당뇨병잡지
CHINES JOURNAL OF DLABETES MELLITUS
2014年
2期
121-125
,共5页
鄞国书%徐冬川%孙如琼%林少达
鄞國書%徐鼕川%孫如瓊%林少達
은국서%서동천%손여경%림소체
(前)肾素受体%氧化应激%脂肪组织%手把区域多肽
(前)腎素受體%氧化應激%脂肪組織%手把區域多肽
(전)신소수체%양화응격%지방조직%수파구역다태
(Pro) renin receptor%Oxidative stress%Adipose tissue%Handle region peptide
目的 探讨手把区域多肽(HRP)及氯沙坦对左旋谷氨酸钠(MSG)大鼠胰岛素敏感性的影响及探讨其对腹腔脂肪组织局部肾素血管紧张素系统(RAS)和还原型烟酰胺腺嘌呤二核苷酸磷酸(NADPH)氧化酶亚单位基因表达的影响.方法 将8周龄体重在250~300 g的MSG大鼠共24只采用完全随机法分为MSG对照组(MSG组,n=6)、HRP干预组(MSG-HRP组,n=6,1.0 mg·d-1·kg-1)、氯沙坦干预组(MSG-L组,n=6,450 mg/L于饮用水中)、HRP及氯沙坦联合干预组(MSG-HRP-L组,n=6),干预4周,正常SD大鼠为对照组(Con组,n=6).12周龄时予以行胰岛素耐量试验评估大鼠胰岛素敏感性,计算胰岛素注射后30 min与0 rain时血糖比值.测定单位质量腹腔脂肪组织(前)肾素、(前)肾素受体[(P)RR]和选择性血管紧张素Ⅱ1型受体(AT1R) mRNA的表达及血管紧张素-Ⅱ(Ang-Ⅱ)蛋白水平,测定NADPH氧化酶亚单位P47phox和P22phoxmRNA的表达情况.采用方差分析及LSD两两比较法进行统计学分析.结果 外源性胰岛素注射后计算30 min血糖与基础血糖的比值,MSG组最高(92%±12%),与Con组(66%±8%)、MSG-HRP组(76%±5%)、MSG-L组(78%±5%)、MSG-HRP-L组(75%±10%)比较均有统计学差异(F=6.875,P<0.05).本研究未能检测到腹腔脂肪组织中(前)肾素mRNA的表达.MSG-HRP组、MSG-L组、MSG-HRP-L组(P) RR mRNA表达量分别是MSG组大鼠的1.92、3.19和1.90倍(F=9.805,P<0.05).MSG-HRP组、MSG-L组、MSG-HRP-L组AT1 R mRNA分别是MSG大鼠组表达量的72%、45%和53%(F=14.508,P<0.05).与MSG组比较,MSG-HRP组脂肪局部Ang-Ⅱ水平下调[分别为(36±8)比(56±4) ng/g蛋白,P<0.05],但是MSG-L组和MSG-HRP-L组水平均明显升高[分别为(79±14)比(70±16)比(56±4) ng/g蛋白,F=14.864,均P<0.05].MSG-HRP组、MSG-L组、MSG-HRP-L组腹腔脂肪组织中P47phox mRNA分别是MSG大鼠组表达量的65%、51%和43%(F=7.082,均P<0.05).p22pho mRNA分别是MSG大鼠组表达量的57%、40%和41%(F=9.810,均P<0.05).结论 HRP和氯沙坦均可改善MSG大鼠胰岛素敏感性,其机制可能是其减少脂肪组织局部Ang-Ⅱ的数量或抑制脂肪组织中局部Ang-Ⅱ的效应,抑制氧化应激,从而改善脂肪胰岛素抵抗.
目的 探討手把區域多肽(HRP)及氯沙坦對左鏇穀氨痠鈉(MSG)大鼠胰島素敏感性的影響及探討其對腹腔脂肪組織跼部腎素血管緊張素繫統(RAS)和還原型煙酰胺腺嘌呤二覈苷痠燐痠(NADPH)氧化酶亞單位基因錶達的影響.方法 將8週齡體重在250~300 g的MSG大鼠共24隻採用完全隨機法分為MSG對照組(MSG組,n=6)、HRP榦預組(MSG-HRP組,n=6,1.0 mg·d-1·kg-1)、氯沙坦榦預組(MSG-L組,n=6,450 mg/L于飲用水中)、HRP及氯沙坦聯閤榦預組(MSG-HRP-L組,n=6),榦預4週,正常SD大鼠為對照組(Con組,n=6).12週齡時予以行胰島素耐量試驗評估大鼠胰島素敏感性,計算胰島素註射後30 min與0 rain時血糖比值.測定單位質量腹腔脂肪組織(前)腎素、(前)腎素受體[(P)RR]和選擇性血管緊張素Ⅱ1型受體(AT1R) mRNA的錶達及血管緊張素-Ⅱ(Ang-Ⅱ)蛋白水平,測定NADPH氧化酶亞單位P47phox和P22phoxmRNA的錶達情況.採用方差分析及LSD兩兩比較法進行統計學分析.結果 外源性胰島素註射後計算30 min血糖與基礎血糖的比值,MSG組最高(92%±12%),與Con組(66%±8%)、MSG-HRP組(76%±5%)、MSG-L組(78%±5%)、MSG-HRP-L組(75%±10%)比較均有統計學差異(F=6.875,P<0.05).本研究未能檢測到腹腔脂肪組織中(前)腎素mRNA的錶達.MSG-HRP組、MSG-L組、MSG-HRP-L組(P) RR mRNA錶達量分彆是MSG組大鼠的1.92、3.19和1.90倍(F=9.805,P<0.05).MSG-HRP組、MSG-L組、MSG-HRP-L組AT1 R mRNA分彆是MSG大鼠組錶達量的72%、45%和53%(F=14.508,P<0.05).與MSG組比較,MSG-HRP組脂肪跼部Ang-Ⅱ水平下調[分彆為(36±8)比(56±4) ng/g蛋白,P<0.05],但是MSG-L組和MSG-HRP-L組水平均明顯升高[分彆為(79±14)比(70±16)比(56±4) ng/g蛋白,F=14.864,均P<0.05].MSG-HRP組、MSG-L組、MSG-HRP-L組腹腔脂肪組織中P47phox mRNA分彆是MSG大鼠組錶達量的65%、51%和43%(F=7.082,均P<0.05).p22pho mRNA分彆是MSG大鼠組錶達量的57%、40%和41%(F=9.810,均P<0.05).結論 HRP和氯沙坦均可改善MSG大鼠胰島素敏感性,其機製可能是其減少脂肪組織跼部Ang-Ⅱ的數量或抑製脂肪組織中跼部Ang-Ⅱ的效應,抑製氧化應激,從而改善脂肪胰島素牴抗.
목적 탐토수파구역다태(HRP)급록사탄대좌선곡안산납(MSG)대서이도소민감성적영향급탐토기대복강지방조직국부신소혈관긴장소계통(RAS)화환원형연선알선표령이핵감산린산(NADPH)양화매아단위기인표체적영향.방법 장8주령체중재250~300 g적MSG대서공24지채용완전수궤법분위MSG대조조(MSG조,n=6)、HRP간예조(MSG-HRP조,n=6,1.0 mg·d-1·kg-1)、록사탄간예조(MSG-L조,n=6,450 mg/L우음용수중)、HRP급록사탄연합간예조(MSG-HRP-L조,n=6),간예4주,정상SD대서위대조조(Con조,n=6).12주령시여이행이도소내량시험평고대서이도소민감성,계산이도소주사후30 min여0 rain시혈당비치.측정단위질량복강지방조직(전)신소、(전)신소수체[(P)RR]화선택성혈관긴장소Ⅱ1형수체(AT1R) mRNA적표체급혈관긴장소-Ⅱ(Ang-Ⅱ)단백수평,측정NADPH양화매아단위P47phox화P22phoxmRNA적표체정황.채용방차분석급LSD량량비교법진행통계학분석.결과 외원성이도소주사후계산30 min혈당여기출혈당적비치,MSG조최고(92%±12%),여Con조(66%±8%)、MSG-HRP조(76%±5%)、MSG-L조(78%±5%)、MSG-HRP-L조(75%±10%)비교균유통계학차이(F=6.875,P<0.05).본연구미능검측도복강지방조직중(전)신소mRNA적표체.MSG-HRP조、MSG-L조、MSG-HRP-L조(P) RR mRNA표체량분별시MSG조대서적1.92、3.19화1.90배(F=9.805,P<0.05).MSG-HRP조、MSG-L조、MSG-HRP-L조AT1 R mRNA분별시MSG대서조표체량적72%、45%화53%(F=14.508,P<0.05).여MSG조비교,MSG-HRP조지방국부Ang-Ⅱ수평하조[분별위(36±8)비(56±4) ng/g단백,P<0.05],단시MSG-L조화MSG-HRP-L조수평균명현승고[분별위(79±14)비(70±16)비(56±4) ng/g단백,F=14.864,균P<0.05].MSG-HRP조、MSG-L조、MSG-HRP-L조복강지방조직중P47phox mRNA분별시MSG대서조표체량적65%、51%화43%(F=7.082,균P<0.05).p22pho mRNA분별시MSG대서조표체량적57%、40%화41%(F=9.810,균P<0.05).결론 HRP화록사탄균가개선MSG대서이도소민감성,기궤제가능시기감소지방조직국부Ang-Ⅱ적수량혹억제지방조직중국부Ang-Ⅱ적효응,억제양화응격,종이개선지방이도소저항.
Objective To investigate the effect of handle region peptide (HRP) on insulin sensitivity,local renin-angiotensin system and subunits of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase in abdominal adipose tissue in the rats neonatally treated with monosodium L-glutamate (MSG).Methods The eight-week-old MSG rats were randomly divided into MSG control group (MSG group,n =6),HRP treated group (MSG-HRP group,n =6,1.0 mg · d-1 · kg-1 with mini-pump),losartan treated group (MSG-L group,n =6,450 mg/L in drinking water) and HRP with losartan combined treated group (MSG-HRP-L group,n =6).The period of treatment is four weeks.Normal SD rats (con group,n =6) served as control.At the age of 12 weeks,insulin tolerance test was performed to evaluate the insulin sensitivity.The blood glucose ratio of 30 min to 0 min after infusion of insulin was calculated.The mRNA levels of (Pro) renin,(Pro) renin receptor ((P) RR),angiotensin type 1 receptor (AT1R) and subunits of NADPH oxidase,including p47phox and p22phox in abdominal adipose tissue were measured by realtime PCR,and the protein level of angiotensin-Ⅱ (Ang-Ⅱ) was measured by ELISA.ANOVA and LSDtest was performed to estimate difference between groups.Results The ratio of blood glucose concentration 30 min after insulin injection to the basic blood glucose concentration was calculated.The MSG group (92%± 12%) had the highest level of the ratio and had statistic difference with the Con group (66% 8%),MSG-HRP group (76% ±5%),MSG-L group (78% ±5%) and MSG-HRP-L group (75% 10%) (F =6.875,all above P < 0.05).The (pro) renin mRNA was not detected in abdominal adipose tissue.The MSG-HRP group,MSG-L group,and MSG-HRP-L group had 1.92,3.19 and 1.90 times (F=9.805,all P < 0.05) of (P) RR mRNA expression respectively and had 72%,45%,and 53% (F =14.508,all P <0.05) of AT1R mRNA expression respectively compared to the MSG group.Compared to the MSG group ((56 ± 4) ng/g protein),local adipose tissue level of Ang-Ⅱ decreased in the MSG-HRP group ((36 ± 8) ng/g protein,P < 0.05),and obviously increased in the MSG-L group ((79 ± 14) ng/g protein,P < 0.05) and MSG-HRP-L group ((70 ± 16) ng/g protein,F =14.864,all above P < 0.05).The MSG-HRP group,MSG-L group and MSG-HRP-L group had 65%,51% and 43% (F =7.082,all above P < 0.05) of p47phox mRNA expression respectively and had 57%,40% and 41% (F =9.810,all above P < 0.05) of p22phox mRNA expression respectively compared to the MSG group.Conclusion Both of HRP and losartan ameliorated insulin sensitivity with the possible mechanism of decreasing the level of Ang-Ⅱ or inhibiting the effect of Ang-Ⅱ in abdominal adipose tissue,and hence inhibiting oxidative stress.