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自噬在多氯联苯118致大鼠甲状腺组织损伤中的作用机制
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作者 王莉 许文立 +1 位作者 朱晓霞 段宇 《山东医药》 CAS 2021年第15期26-31,共6页
目的探讨自噬在慢性低浓度[0~1 000μg/(kg·d)]多氯联苯118(PCB118)导致大鼠甲状腺组织损伤中的作用机制。方法将40只雄性Wistar大鼠随机分为A、B、C、D组,每周腹腔注射0、10、100、1 000μg/(kg·d)PCB118 5次,共13周。PCB11... 目的探讨自噬在慢性低浓度[0~1 000μg/(kg·d)]多氯联苯118(PCB118)导致大鼠甲状腺组织损伤中的作用机制。方法将40只雄性Wistar大鼠随机分为A、B、C、D组,每周腹腔注射0、10、100、1 000μg/(kg·d)PCB118 5次,共13周。PCB118处理结束后,处死大鼠取甲状腺组织,用透射电子显微镜观察大鼠甲状腺组织超微结构。采用蛋白免疫印迹法检测甲状腺组织自噬相关蛋白LC3、P62、BECLIN1及β-Ⅲ型微管蛋白(Tubb3)/死亡相关蛋白激酶2(DAPK2)-通路相关蛋白[Tubb3、DAPK2、肌球蛋白调节轻链(MRLC)、磷酸化MRLC(p-MRLC)、自噬相关基因9A(ATG9A)]。采用实时荧光定量PCR法检测Tubb3/DAPK2-通路相关基因[Tubb3、DAPK2、非肌肉肌球蛋白重链IIA(NMMHC-ⅡA)、ATG9A]。结果与A组比较,B、C、D组甲状腺滤泡细胞损伤、部分空泡化,线粒体密度下降、嵴膜消失,伴内质网扩张,且上述改变在C组最为明显,C、D组出现典型的自噬小体。与A组比较,B组LC3Ⅱ/LC3Ⅰ升高(P均<0.05);C、D组LC3Ⅱ/LC3Ⅰ、BECLIN1蛋白表达升高,P62蛋白表达降低(P<0.01)。与B组比较,C组BECLIN1蛋白表达升高(P均<0.01);D组LC3Ⅱ/LC3Ⅰ、BECLIN1蛋白表达升高,P62蛋白表达降低(P均<0.05)。与C组比较,D组LC3Ⅱ/LC3Ⅰ、BECLIN1蛋白表达升高(P均0.01)。与A组比较,C、D组Tubb3蛋白表达降低(P均<0.01),DAPK2蛋白表达、p-MRLC/MRLC升高(P均<0.05)。与B组比较,C组Tubb3蛋白表达降低,DAPK2蛋白表达升高(P均<0.05);D组Tubb3蛋白表达降低,DAPK2、MRLC、p-MRLC蛋白表达及p-MRLC/MRLC升高(P均<0.05)。与C组比较,D组DAPK2蛋白表达降低,MRLC、p-MRLC蛋白表达及p-MRLC/MRLC升高(P均<0.05)。与A组比较,B组Tubb3 mRNA降低,DAPK2、ATG9A mRNA升高(P均<0.05);C组Tubb3 mRNA降低,DAPK2、NMMHC-ⅡA、ATG9A mRNA升高(P均<0.05);D组Tubb3表达降低,NMMHC-ⅡA、ATG9A mRNA升高(P均<0.05)。与B组比较,C组DAPK2、ATG9A mRNA升高(P均<0.01)。与C组比较,D组DAPK2、ATG9A mRNA降低(P均<0.05)。结论自噬在慢性低浓度PCB118导致大鼠甲状腺组织损伤中起重要作用,其作用机制可能与Tubb3/DAPK2-相关信号通路有关。 展开更多
关键词 环境内分泌干扰物 多氯联苯118 自噬 甲状腺自噬 Tubb3/DAPK2-通路
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Effects of herbal cake-partitioned moxibustion on the expression of thyroid autophagy-related factors LC3B and Beclin-1 in rats with autoimmune thyroiditis
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作者 CHEN Kexu ZHAO Jimeng +8 位作者 QIAO Yu ZHU Lu HUANG Yan LIU Yanan ZHENG Handan LIU Huirong CUI Yunhua WU Huangan YANG Yanping 《Journal of Acupuncture and Tuina Science》 CSCD 2022年第6期453-463,共11页
Objective:To observe the anti-inflammatory effect,as well as the effect on the expression of microtubule-associated protein light chain 3B(LC3B)and Beclin-1 of herbal cake-partitioned moxibustion in rats with experime... Objective:To observe the anti-inflammatory effect,as well as the effect on the expression of microtubule-associated protein light chain 3B(LC3B)and Beclin-1 of herbal cake-partitioned moxibustion in rats with experimental autoimmune thyroiditis(EAT).Methods:Female Sprague-Dawley rats were randomly divided into a normal group and a modeling group.The EAT rat model was prepared by a combination of antigen immunization plus iodine agent induction.After the model was prepared,rats in the modeling group were randomly and equally divided into a model group and a herbal cake-partitioned moxibustion group.In the herbal cake-partitioned moxibustion group,moxibustion was alternately applied to two groups of points[Dazhui(GV14)-Mingmen(GV4)and Tiantu(CV22)-Guanyuan(CV4)],and the treatment continued for 30 d.Rats in the normal and model groups were only fixed identically without intervention.Histopathological manifestations of thyroid glands were observed by hematoxylin-eosin staining;the concentrations of thyroid peroxidase antibodies(TPOAb),thyroglobulin antibodies(TGAb),interleukin-1β(IL-1β),interleukin-6(IL-6),and tumor necrosis factor-α(TNF-α)were detected by enzyme-linked immunosorbent assay;real-time fluorescence quantitative polymerase chain reaction and immunohistochemistry were used to detect the mRNA and protein expression of autophagy-related factors LC3B and Beclin-1 in thyroid tissue.Results:There were massive follicular destruction,lymphocytic infiltration,and interstitial fibrous tissue hyperplasia of the thyroid glands in the model group.Some follicles of the thyroid glands were destroyed with few lymphocyte infiltrations and fibrous tissue hyperplasia in the moxibustion group.Compared with the normal group,the concentrations of serum TPOAb,TGAb,IL-1β,IL-6,and TNF-αwere increased in the model rats(P<0.05);the mRNA and protein expression levels of LC3B and Beclin-1 in thyroid tissue were reduced in the model group(P<0.05).Compared with the model group,the concentrations of serum TPOAb,TGAb,IL-1β,IL-6,and TNF-αwere reduced in the herbal cake-partitioned moxibustion group(P<0.05);the mRNA and protein expression levels of LC3B and Beclin-1 in thyroid tissue were increased in the herbal cake-partitioned moxibustion group(P<0.05).The mRNA and protein expression of LC3B and Beclin-1 in thyroid tissue was negatively correlated with the serum levels of TPOAb and TGAb.Conclusion:Herbal cake-partitioned moxibustion reduces the inflammatory response in the thyroid glands of EAT rats and lowers the levels of serum TPOAb and TGAb.This may be related to the regulation of mRNA and protein expression of the autophagy-associated factors LC3B and Beclin-1 in rat thyroid tissue. 展开更多
关键词 Moxibustion Therapy Medicinal Cake-partitioned Moxibustion Thyroiditis Autoimmune AUTOPHAGY Points Conception Vessel Points Governor Vessel RATS
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