嘌呤能离子通道型受体7(purinergic ligand-gated ion channel 7receptor,P2X7R)是ATP门控的,非选择性的阳离子通道,属于嘌呤受体P2X家族。P2X7R激活多种胞内信号通路,参与机体免疫反应、神经递质释放、氧化应激及细胞增殖和凋亡等多种...嘌呤能离子通道型受体7(purinergic ligand-gated ion channel 7receptor,P2X7R)是ATP门控的,非选择性的阳离子通道,属于嘌呤受体P2X家族。P2X7R激活多种胞内信号通路,参与机体免疫反应、神经递质释放、氧化应激及细胞增殖和凋亡等多种生理功能。研究证实,P2X7R在自身免疫性疾病的发生、发展中也有一定的影响和作用。现就P2X7R与系统性红斑狼疮、多发性硬化、银屑病、干燥综合征、类风湿性关节炎等自身免疫性疾病关系的研究进展作综述。展开更多
Aim To investigate the protective effects of gentiopicroside （GPS） on acute alcohol-induced fatty liver.Methods Mice were treated with ethanol （5 g · kg^-11 of body weight） by gavage every 12 h for a total of...Aim To investigate the protective effects of gentiopicroside （GPS） on acute alcohol-induced fatty liver.Methods Mice were treated with ethanol （5 g · kg^-11 of body weight） by gavage every 12 h for a total of three do- ses to induce acute fatty liver. GPS （40 or 80 mg · kg^-1 ） was garaged with ethanol simultaneously for three doses. Administration of GPS significantly prevented the increases of serum ALT and AST caused by ethanol, as well as se- rum and hepatic TG. Results GPS could significantly prevent ethanol-induced hepatic steatosis and necrosis by H＆E and Oil Red O staining. GPS also significantly inhibited lipogenic genes including sterol regulatory element binding transcription factor 1 （ SREBP-1 ）, fatty acid synthase （FASN） and acetyl-CoA carboxylase （ACC） in eth- anol-treated mice. Additionally, GPS possessed the ability to prevent ethanol-induced acute liver steatosis, possibly through inducing the phosphorylation of AMP-activated protein kinase （AMPK） and liver kinase B1 （LKB1）. Af- ter treatment with GPS, peroxisome proliferator-activated receptor eL （PPARoL） protein expression in mouse liver was recovered as that level of normal mice. Ethanol treatment evoked P2X7r and caspase-1 protein expression, while GPS significantly suppressed those protein expressions. GPS may be developed as a potential therapeutic can- didate for ethanol-induced hepatic steatosis and inflammation.展开更多
Liver X receptors(LXRs)are known as key transcription factors in lipid metabolism and have been reported to play an important role in T-cell proliferation.However,whether LXRs play a role in thymocyte development rema...Liver X receptors(LXRs)are known as key transcription factors in lipid metabolism and have been reported to play an important role in T-cell proliferation.However,whether LXRs play a role in thymocyte development remains largely unknown.Here,we demonstrated that LXRβdeficiency caused a reduction in single-positive(SP)thymocytes,whereas the transitions from the double-negative to SP stage were normal.Meanwhile,LXRβ-null SP thymocytes exhibited increased apoptosis and impairment of the IL-7Rα-Bcl2 axis.In addition,the LXR agonist T0901317 promoted the survival of SP thymocytes with enhanced IL-7Rαexpression in wild-type mice but not in LXRβ-deficient mice.Mechanistically,LXRβpositively regulated the expression of IL-7Rαvia direct binding to the Il7r allele in SP thymocytes,and forced expression of IL-7Rαor Bcl2 restored the survival of LXRβ-defective SP thymocytes.Thus,our results indicate that LXRβfunctions as an important transcription factor upstream of IL-7Rαto promote the survival of SP thymocytes.展开更多
文摘嘌呤能离子通道型受体7(purinergic ligand-gated ion channel 7receptor,P2X7R)是ATP门控的,非选择性的阳离子通道,属于嘌呤受体P2X家族。P2X7R激活多种胞内信号通路,参与机体免疫反应、神经递质释放、氧化应激及细胞增殖和凋亡等多种生理功能。研究证实,P2X7R在自身免疫性疾病的发生、发展中也有一定的影响和作用。现就P2X7R与系统性红斑狼疮、多发性硬化、银屑病、干燥综合征、类风湿性关节炎等自身免疫性疾病关系的研究进展作综述。
文摘Aim To investigate the protective effects of gentiopicroside （GPS） on acute alcohol-induced fatty liver.Methods Mice were treated with ethanol （5 g · kg^-11 of body weight） by gavage every 12 h for a total of three do- ses to induce acute fatty liver. GPS （40 or 80 mg · kg^-1 ） was garaged with ethanol simultaneously for three doses. Administration of GPS significantly prevented the increases of serum ALT and AST caused by ethanol, as well as se- rum and hepatic TG. Results GPS could significantly prevent ethanol-induced hepatic steatosis and necrosis by H＆E and Oil Red O staining. GPS also significantly inhibited lipogenic genes including sterol regulatory element binding transcription factor 1 （ SREBP-1 ）, fatty acid synthase （FASN） and acetyl-CoA carboxylase （ACC） in eth- anol-treated mice. Additionally, GPS possessed the ability to prevent ethanol-induced acute liver steatosis, possibly through inducing the phosphorylation of AMP-activated protein kinase （AMPK） and liver kinase B1 （LKB1）. Af- ter treatment with GPS, peroxisome proliferator-activated receptor eL （PPARoL） protein expression in mouse liver was recovered as that level of normal mice. Ethanol treatment evoked P2X7r and caspase-1 protein expression, while GPS significantly suppressed those protein expressions. GPS may be developed as a potential therapeutic can- didate for ethanol-induced hepatic steatosis and inflammation.
基金This work was supported by grants from the National Key Research and Development Program of China(No.2016YFA0502203 to X.Z.and No.2016YFA0502204 to Y.W.)the National Natural Science Foundation of China(No.81571537 to T.Z.,No.31770949 to X.Z.,No.31770972 to Z.X.,and No.81571604 to J.Z.)the Chongqing Basic and Frontier Research Project(No.cstc2015jcyjBX0086 to H.He.).
文摘Liver X receptors(LXRs)are known as key transcription factors in lipid metabolism and have been reported to play an important role in T-cell proliferation.However,whether LXRs play a role in thymocyte development remains largely unknown.Here,we demonstrated that LXRβdeficiency caused a reduction in single-positive(SP)thymocytes,whereas the transitions from the double-negative to SP stage were normal.Meanwhile,LXRβ-null SP thymocytes exhibited increased apoptosis and impairment of the IL-7Rα-Bcl2 axis.In addition,the LXR agonist T0901317 promoted the survival of SP thymocytes with enhanced IL-7Rαexpression in wild-type mice but not in LXRβ-deficient mice.Mechanistically,LXRβpositively regulated the expression of IL-7Rαvia direct binding to the Il7r allele in SP thymocytes,and forced expression of IL-7Rαor Bcl2 restored the survival of LXRβ-defective SP thymocytes.Thus,our results indicate that LXRβfunctions as an important transcription factor upstream of IL-7Rαto promote the survival of SP thymocytes.
