CAJ | 학술논문

目的观察碘过量对自身免疫性疾病敏感品系NOD鼠和非敏感品系Balb/c鼠甲状腺细胞凋亡相关基因肿瘤坏死因子的相关凋亡诱导配体(tumor necrosis factor-related apoptosis-inducing ligand, TRAIL)和其受体TRAIL刺激性受体1(TRAIL-sR1)表达的影响,了解碘过量诱导实验性自身免疫性甲状腺炎(EAT)发病过程中TRAIL和TRAIL-sR1的作用机制.方法 6～7周龄雌性NOD鼠和Balb/c鼠各16只,按体质量各随机分为对照组和碘过量(HI)组,每组8只.对照组饮高压灭菌水,HI组饮0.05%NaI添加水,饲养8周后处死.测量甲状腺相对质量,进行甲状腺组织形态学观察,测量血清甲状腺素(TT4)和甲状腺刺激激素(TSH),检测甲状腺滤泡上皮细胞凋亡情况,应用实时定量PcR(real time PCR)方法检测TRAIL和TRAIL-sR1 mRNA表达情况.结果 NOD鼠HI组甲状腺相对质量[(104.8±14.5)mg/kg]高于对照组[(71.8±20.4)mg/kg],血清TT4水平[(30.77±3.59)mmol/L]低于对照组[(36.43±2.66)mmol/L],TSH水平[(6.98±0.66)μg/L]高于对照组[(5.55±0.56)μg/L],组间比较差异均有统计学意义(t值分别为7.773、-9.526、-4.458,P均<0.05).HI组甲状腺出现滤泡扩张、胶质潴留及明显的淋巴细胞浸润伴灶性纤维化.Balb/c鼠川组甲状腺相对质量[(155.8±20.8)mg/kg]高于对照组[(105.1±22.0)mg/kg],血清TT4水平[(19.75±3.32)mmol/L]低于对照组[(23.46±6.21)mmol/L],TSH水平[(4.14±1.71)μg/L]高于对照组[(3.55±1.41)μg/L],组间比较差异均有统计学意义(t值分别为7.554、-7.239、3.140,P均<0.05);HI组甲状腺仅有甲状腺滤泡扩张,胶质潴留,而未见明显的淋巴细胞浸润.HI组NOD鼠和Balb/c鼠甲状腺滤泡上皮细胞的凋亡指数(3.97±0.91、1.05±0.45)分别高于对照组(0.21±0.15、0.10±0.03),组间比较差异均有统计学意义(t值分别为-7.167、-17.772,P均<0.05),Balb/c鼠HI组的甲状腺滤泡上皮细胞的凋亡指数低于NOD鼠HI组,组间比较差异有统计学意义(t=-7.625,P<0.05).NOD鼠HI组TRAIL mRNA表达水平(0.018 88±0.005 77)高于对照组(0.00961±0.005 91),组间比较差异有统计学意义(t=-2.710,P<0.05);Balb/c鼠HI组TRAIL表达水平(0.001 24±0.000 46)与对照组(0.000 59±0.000 39)比较,差异无统计学意义(t=-1.940,P>0.05);NOD鼠和Balb/c鼠HI组的TRAIL-sR1 mRNA表达水平(0.000 53±0.000 15、0.000 42±0.000 09)均高于对照组(0.000 28±0.000 05、0.000 17±0.000 06),组间比较差异有统计学意义(t值分别为3.050,3.990,P均<0.05),Balb/c鼠HI组的TRAIL和TRAIL-sR1的mRNA表达水平均低于NOD鼠HI组,组间比较差异均有统计学意义(t值分别为-3.370、-4.760,P均<0.05).结论碘过量可使NOD和Balb/c鼠发生胶质潴留性甲状腺肿,并可造成NOD鼠甲状腺发生明显的炎症反应.TRAIL和TRAIL-sR1表达水平升高是碘过量导致甲状腺滤泡上皮凋亡和炎症发生的分子基础之一.遗传在甲状腺炎的发病过程中起到至关重要的作用. 目的觀察碘過量對自身免疫性疾病敏感品繫NOD鼠和非敏感品繫Balb/c鼠甲狀腺細胞凋亡相關基因腫瘤壞死因子的相關凋亡誘導配體(tumor necrosis factor-related apoptosis-inducing ligand, TRAIL)和其受體TRAIL刺激性受體1(TRAIL-sR1)錶達的影響,瞭解碘過量誘導實驗性自身免疫性甲狀腺炎(EAT)髮病過程中TRAIL和TRAIL-sR1的作用機製.方法 6～7週齡雌性NOD鼠和Balb/c鼠各16隻,按體質量各隨機分為對照組和碘過量(HI)組,每組8隻.對照組飲高壓滅菌水,HI組飲0.05%NaI添加水,飼養8週後處死.測量甲狀腺相對質量,進行甲狀腺組織形態學觀察,測量血清甲狀腺素(TT4)和甲狀腺刺激激素(TSH),檢測甲狀腺濾泡上皮細胞凋亡情況,應用實時定量PcR(real time PCR)方法檢測TRAIL和TRAIL-sR1 mRNA錶達情況.結果 NOD鼠HI組甲狀腺相對質量[(104.8±14.5)mg/kg]高于對照組[(71.8±20.4)mg/kg],血清TT4水平[(30.77±3.59)mmol/L]低于對照組[(36.43±2.66)mmol/L],TSH水平[(6.98±0.66)μg/L]高于對照組[(5.55±0.56)μg/L],組間比較差異均有統計學意義(t值分彆為7.773、-9.526、-4.458,P均<0.05).HI組甲狀腺齣現濾泡擴張、膠質潴留及明顯的淋巴細胞浸潤伴竈性纖維化.Balb/c鼠川組甲狀腺相對質量[(155.8±20.8)mg/kg]高于對照組[(105.1±22.0)mg/kg],血清TT4水平[(19.75±3.32)mmol/L]低于對照組[(23.46±6.21)mmol/L],TSH水平[(4.14±1.71)μg/L]高于對照組[(3.55±1.41)μg/L],組間比較差異均有統計學意義(t值分彆為7.554、-7.239、3.140,P均<0.05);HI組甲狀腺僅有甲狀腺濾泡擴張,膠質潴留,而未見明顯的淋巴細胞浸潤.HI組NOD鼠和Balb/c鼠甲狀腺濾泡上皮細胞的凋亡指數(3.97±0.91、1.05±0.45)分彆高于對照組(0.21±0.15、0.10±0.03),組間比較差異均有統計學意義(t值分彆為-7.167、-17.772,P均<0.05),Balb/c鼠HI組的甲狀腺濾泡上皮細胞的凋亡指數低于NOD鼠HI組,組間比較差異有統計學意義(t=-7.625,P<0.05).NOD鼠HI組TRAIL mRNA錶達水平(0.018 88±0.005 77)高于對照組(0.00961±0.005 91),組間比較差異有統計學意義(t=-2.710,P<0.05);Balb/c鼠HI組TRAIL錶達水平(0.001 24±0.000 46)與對照組(0.000 59±0.000 39)比較,差異無統計學意義(t=-1.940,P>0.05);NOD鼠和Balb/c鼠HI組的TRAIL-sR1 mRNA錶達水平(0.000 53±0.000 15、0.000 42±0.000 09)均高于對照組(0.000 28±0.000 05、0.000 17±0.000 06),組間比較差異有統計學意義(t值分彆為3.050,3.990,P均<0.05),Balb/c鼠HI組的TRAIL和TRAIL-sR1的mRNA錶達水平均低于NOD鼠HI組,組間比較差異均有統計學意義(t值分彆為-3.370、-4.760,P均<0.05).結論碘過量可使NOD和Balb/c鼠髮生膠質潴留性甲狀腺腫,併可造成NOD鼠甲狀腺髮生明顯的炎癥反應.TRAIL和TRAIL-sR1錶達水平升高是碘過量導緻甲狀腺濾泡上皮凋亡和炎癥髮生的分子基礎之一.遺傳在甲狀腺炎的髮病過程中起到至關重要的作用.
목적 관찰전과량대자신면역성질병민감품계NOD서화비민감품계Balb/c서갑상선세포조망상관기인종류배사인자적상관조망유도배체(tumor necrosis factor-related apoptosis-inducing ligand, TRAIL)화기수체TRAIL자격성수체1(TRAIL-sR1)표체적영향,료해전과량유도실험성자신면역성갑상선염(EAT)발병과정중TRAIL화TRAIL-sR1적작용궤제.방법 6～7주령자성NOD서화Balb/c서각16지,안체질량각수궤분위대조조화전과량(HI)조,매조8지.대조조음고압멸균수,HI조음0.05%NaI첨가수,사양8주후처사.측량갑상선상대질량,진행갑상선조직형태학관찰,측량혈청갑상선소(TT4)화갑상선자격격소(TSH),검측갑상선려포상피세포조망정황,응용실시정량PcR(real time PCR)방법검측TRAIL화TRAIL-sR1 mRNA표체정황.결과 NOD서HI조갑상선상대질량[(104.8±14.5)mg/kg]고우대조조[(71.8±20.4)mg/kg],혈청TT4수평[(30.77±3.59)mmol/L]저우대조조[(36.43±2.66)mmol/L],TSH수평[(6.98±0.66)μg/L]고우대조조[(5.55±0.56)μg/L],조간비교차이균유통계학의의(t치분별위7.773、-9.526、-4.458,P균<0.05).HI조갑상선출현려포확장、효질저류급명현적림파세포침윤반조성섬유화.Balb/c서천조갑상선상대질량[(155.8±20.8)mg/kg]고우대조조[(105.1±22.0)mg/kg],혈청TT4수평[(19.75±3.32)mmol/L]저우대조조[(23.46±6.21)mmol/L],TSH수평[(4.14±1.71)μg/L]고우대조조[(3.55±1.41)μg/L],조간비교차이균유통계학의의(t치분별위7.554、-7.239、3.140,P균<0.05);HI조갑상선부유갑상선려포확장,효질저류,이미견명현적림파세포침윤.HI조NOD서화Balb/c서갑상선려포상피세포적조망지수(3.97±0.91、1.05±0.45)분별고우대조조(0.21±0.15、0.10±0.03),조간비교차이균유통계학의의(t치분별위-7.167、-17.772,P균<0.05),Balb/c서HI조적갑상선려포상피세포적조망지수저우NOD서HI조,조간비교차이유통계학의의(t=-7.625,P<0.05).NOD서HI조TRAIL mRNA표체수평(0.018 88±0.005 77)고우대조조(0.00961±0.005 91),조간비교차이유통계학의의(t=-2.710,P<0.05);Balb/c서HI조TRAIL표체수평(0.001 24±0.000 46)여대조조(0.000 59±0.000 39)비교,차이무통계학의의(t=-1.940,P>0.05);NOD서화Balb/c서HI조적TRAIL-sR1 mRNA표체수평(0.000 53±0.000 15、0.000 42±0.000 09)균고우대조조(0.000 28±0.000 05、0.000 17±0.000 06),조간비교차이유통계학의의(t치분별위3.050,3.990,P균<0.05),Balb/c서HI조적TRAIL화TRAIL-sR1적mRNA표체수평균저우NOD서HI조,조간비교차이균유통계학의의(t치분별위-3.370、-4.760,P균<0.05).결론 전과량가사NOD화Balb/c서발생효질저류성갑상선종,병가조성NOD서갑상선발생명현적염증반응.TRAIL화TRAIL-sR1표체수평승고시전과량도치갑상선려포상피조망화염증발생적분자기출지일.유전재갑상선염적발병과정중기도지관중요적작용.
Objective To investigate the influence of iodine excess on expression of TRAIl/TRAIL-sR1 in NOD and Balb/c mice and to study the effect of TRAIl/TRAIL-sR1 on the pathogenesis of experimental autoimmune thyroiditis(EAT). Methods Both Balb/c and NOD mice were divided randomly into control and iodine excess group by feeding with water containing no NaI or 0.05% Nal. The mice were sacrificed after 8 weeks. TRAIL and TRAIL-sR1 mRNA levels were detected by RT-PCR. The function, morphology and apoptosis of thyroids were also observed by ELISA and Tunnel stain. Results Treated by HI, enlarged follicles and flattened epithelium by accumulation of colloid were found in thyroids of both NOD and Balb/c mice. But significant lymphoid cell infiltration and local fibrosis were only found in thyroids of NOD HI group. The relative weight of thyroids of NOD mice in HI group[(104.8±14.5)mg/kg]was heavier than that of control group [(71.8±20.4)mg/kg]. The level of TT4 declined in HI group[(30.77±3.59)mmol/L]compared with control group[(36.43±2.66)mmol/L], meanwhile, the level of TSH was higher in HI group[(6.98±0.66)μg/L]than that in control group [(5.55±0.56)μg/L]. The difference being statistically significant(t=7.773,-9.526,-4.458, all P < 0.05). The relative weight of thyroids of Balb/c mice of HI group[(155.8±20.8)mg/kg]also heavier than that of control group [(105.1±22.0) mg/kg]. The level of TT4 droped in HI group [(19.75±3.32) mmoL/L]was higher than that in control group[(23.46±6.21)mmoL/L], the level of TSH in HI group[(4.14±1.71)μg/L]was higher than that in control group[(3.55±1.41)μg/L], the difference being statistically significant(t=7.554,-7.239,3.140, all P< 0.05). A great deal of apoptotie ceils observed in NOD (3.97±0.91) and Balb/c mice (1.05±0.45) by Tunnel stain were greater than control groups (0.21±0.15, 0.10±0.03), the difference being statistically significant in beth of the two species(t=-7.167,-17.772, both P < 0.05). The apoptosis index of thyroid follicular epithelium in NOD was obviously higher than Balb/c(t=-7.625, P<0.05). The level of TRAIL mRNA did not remarkably change in Balb/c between control group(0.000 59±0.000 39) and HI group(0.001 24±0.000 46, t=-1.940, P>0.05), but it increased apparently in NOD mice HI group(0.018 88±0.005 77) than that of control group(0.009 61± 0.00591, t=-2.71, P<0.05). The level of the expression of TRAIL-sR1 mRNA increased in HI groups of NOD (0.000 53±0.000 15) and Balb/c mice(0.000 42±0.000 09) than that in control groups of NOD(0.000 28± 0.000 05) and Balb/c mice (0.000 17±0.000 06) and the differences were statistically significant between the two species(t=3.050,3.990, all P<0.05). The differences of the expression of TRAIL and TRAIL-sR1 mRNA between the two species were significant(t=-3.37,-4.76, all P<0.05). Conclusions Iodine excess induces colloid goiter in beth species of mice and thyroiditis in NOD mice. The increase of TRAIL and TRAIL-sR1 influenced by iodine excess is one of the molecular bases of follicular epithelium apoptosis and inflammation in thyroids. Genetic factor is a key factor in the pathogenesis of thyroiditis.