CAJ | 학술논문

目的：探讨利拉鲁肽是否能够抑制糖尿病大鼠肾组织局部肾素-血管紧张素系统（RAS），进而下调转化生长因子（TGF）-β1表达。方法给予4周龄雄性Wistar大鼠高糖高脂饲料喂养联合小剂量链脲佐菌素鼠尾静脉注射建立糖尿病大鼠模型20只，采用随机数字表法分为糖尿病组和利拉鲁肽组，每组10只，同时设对照组10只。利拉鲁肽组予以利拉鲁肽（400μg· kg-1· d-1）皮下注射，对照组和糖尿病组大鼠给予等量生理盐水皮下注射。12周后，应用实时定量聚合酶链反应（PCR）、Western blotting法检测比较各组大鼠肾组织血管紧张素Ⅱ1型受体（AT1R）和TGF-β1表达的变化，酶联免疫吸附实验检测各组肾组织血管紧张素（ Ang）Ⅱ的表达，Masson染色观察各组大鼠肾组织胶原沉积情况。采用单因素方差分析比较组间差异，两两比较采用LSD检验。结果 Masson染色显示，糖尿病组大鼠肾组织胶原纤维沉积对照组明显增多，利拉鲁肽组大鼠肾组织胶原纤维沉积较糖尿病组少。糖尿病组大鼠肾组织AngⅡ表达显著高于对照组（t＝3.444，P＜0.05），利拉鲁肽组大鼠肾组织AngⅡ表达则较糖尿病组显著降低（ t＝2.614，P＜0.05）。糖尿病组大鼠肾组织AT1R、TGF-β1 mRNA和蛋白表达显著高于对照组（t＝4.084、3.714、9.381、6.408，均P＜0.05）。利拉鲁肽组大鼠肾组织AT1R、TGF-β1mRNA和蛋白表达显著低于糖尿病组（ t＝3.487、2.907、5.033、2.295，均P＜0.05）。结论利拉鲁肽可抑制糖尿病大鼠肾组织TGF-β1的表达发挥肾保护作用，可能与其抑制肾组织局部RAS活性有关。
목적：탐토리랍로태시부능구억제당뇨병대서신조직국부신소-혈관긴장소계통（RAS），진이하조전화생장인자（TGF）-β1표체。방법급여4주령웅성Wistar대서고당고지사료위양연합소제량련뇨좌균소서미정맥주사건립당뇨병대서모형20지，채용수궤수자표법분위당뇨병조화리랍로태조，매조10지，동시설대조조10지。리랍로태조여이리랍로태（400μg· kg-1· d-1）피하주사，대조조화당뇨병조대서급여등량생리염수피하주사。12주후，응용실시정량취합매련반응（PCR）、Western blotting법검측비교각조대서신조직혈관긴장소Ⅱ1형수체（AT1R）화TGF-β1표체적변화，매련면역흡부실험검측각조신조직혈관긴장소（ Ang）Ⅱ적표체，Masson염색관찰각조대서신조직효원침적정황。채용단인소방차분석비교조간차이，량량비교채용LSD검험。결과 Masson염색현시，당뇨병조대서신조직효원섬유침적대조조명현증다，리랍로태조대서신조직효원섬유침적교당뇨병조소。당뇨병조대서신조직AngⅡ표체현저고우대조조（t＝3.444，P＜0.05），리랍로태조대서신조직AngⅡ표체칙교당뇨병조현저강저（ t＝2.614，P＜0.05）。당뇨병조대서신조직AT1R、TGF-β1 mRNA화단백표체현저고우대조조（t＝4.084、3.714、9.381、6.408，균P＜0.05）。리랍로태조대서신조직AT1R、TGF-β1mRNA화단백표체현저저우당뇨병조（ t＝3.487、2.907、5.033、2.295，균P＜0.05）。결론리랍로태가억제당뇨병대서신조직TGF-β1적표체발휘신보호작용，가능여기억제신조직국부RAS활성유관。
Objective To explore the effects of glucagon-like peptide-1 receptor analog liraglutide ( LR) on the expression of local renin-angiotensin system ( RAS) and transforming growth factor ( TGF)-β1 in renal tissue of diabetic rats.Methods Twenty Wistar rats diabetes models were divided into , diabetic group ( DM) , and LR-treated group ( LR) according to the table of random number after induced by feeding with high-sugary and high-fat diet and injecting of a low dose of streptozotocin into the caudal vein for 8 weeks.And ten healthy Wistar rats were set as normal control ( NC).After the establishment of diabetes model, liraglutide (400 μg· kg-1 · d-1 ) was administered by subcutaneous injection for 12 weeks in LR group.And the rats in NC and DM group were injected with saline in the same way.At the end of the trial , the mRNA expression levels of angiotensin Ⅱ(AngⅡ) type 1 receptor (AT1R) and TGF-β1 were detected by real-time quantitative polymerase chain reaction (RT-q PCR), the protein expression levels of AT1R and TGF-β1 were detected by Western blotting ( WB ) and the protein expression of AngⅡ was detected by enzyme-linked immunosorbent assay ( ELISA).Masson staining was used to observe the collagen deposition of renal tissue in rats of different groups.Single factor analysis of variance ( ANOVA) was applied in data comparison among the groups , and LSD test were used to analyze the difference between two groups.Results Masson staining showed that DM group had more collagen than NC group in renal tissue , but it was alleviated in LR group.Compared with that in NC group , expressions of AngⅡin renal tissue of DM group was elevated significantly(t=3.444, P<0.05), and it was down-regulated significantly in LR group thant that in DM group(t=2.614, P<0.05).The mRNA and protein expression of AT1R and TGF-β1 in renal tissue in DM group were significantly higher than those in NC group ( t=4.084, 3.714, 9.381, 6.408, all P<0.05), and all were down-regulated significantly in LR group when compared with those in DM group (t=3.487, 2.907, 5.033, 2.295, all P<0.05).Conclusion Liraglutide plays a role of organ-protecting by inhibiting the expression of TGF-β1 in renal tissue of diabetic rats , and this may be related with the down-regulating of local RAS.