Shanghai Key Laboratory of Bioactive Small Molecules, School of Pharmacy, Fudan University, Shanghai, China.
China State Institute of Pharmaceutical Industry, Shanghai, China.
Pharm Biol. 2022 Dec;60(1):1169-1176. doi: 10.1080/13880209.2022.2080234.
-Propargyl-cysteine (SPRC), an endogenous HS modulator, exerts anti-inflammatory effects on cardiovascular and neurodegenerative disease, but it remains unknown whether SPRC can prevent autoimmune hepatitis.
To evaluate the preventive effect of SPRC on concanavalin A (Con A)-induced liver injury and uncover the underlying mechanisms.
Mice were randomly divided into five groups: control, Con A, SPRC (5 and 10 mg/kg injected intravenously once a day for 7 days), and propargylglycine (PAG; 50 mg/kg injected intraperitoneally 0.5 h before SPRC for 7 days). All mice except the controls were intravenously injected with Con A (20 mg/kg) on day 7. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were evaluated using kits. Inflammatory cytokines (TNF-α and IFN-γ) in the blood and in the liver were detected by ELISA Kit and real-time PCR, respectively. The expression of mitogen-activated protein kinase (MAPK) pathway proteins (p-JNK and p-Akt) and apoptosis proteins (Bax and Bcl-2) was detected using western blotting.
SPRC reduced the levels of AST ( < 0.05) and ALT ( < 0.01) and decreased the release of the inflammatory cytokines. Mechanistically, SPRC increased HS level ( < 0.05) and promoted cystathionine γ-lyase (CSE) expression ( < 0.05). SPRC inhibited the MAPK pathway activation and the apoptosis pathway. All the effects of SPRC were blocked by the CSE inhibitor PAG.
SPRC prevents Con A-induced liver injury in mice by promoting CSE expression and producing endogenous HS. The mechanisms include reducing the release of inflammatory cytokines, attenuating MAPK pathway activation, and alleviating apoptosis.
-丙炔半胱氨酸（SPRC），一种内源性 HS 调节剂，对心血管和神经退行性疾病具有抗炎作用，但尚不清楚 SPRC 是否可预防自身免疫性肝炎。
评估 SPRC 对刀豆蛋白 A（Con A）诱导的肝损伤的预防作用，并揭示其潜在机制。
将小鼠随机分为五组：对照组、Con A 组、SPRC（每天静脉注射 5 和 10mg/kg，连续 7 天）组和炔丙基甘氨酸（PAG；SPRC 前 0.5h 腹腔注射 50mg/kg，连续 7 天）组。除对照组外，所有小鼠均在第 7 天静脉注射 Con A（20mg/kg）。使用试剂盒检测丙氨酸氨基转移酶（ALT）和天冬氨酸氨基转移酶（AST）水平。通过 ELISA 试剂盒和实时 PCR 分别检测血液和肝脏中的炎症细胞因子（TNF-α和 IFN-γ）。使用 Western blot 检测丝裂原活化蛋白激酶（MAPK）途径蛋白（p-JNK 和 p-Akt）和凋亡蛋白（Bax 和 Bcl-2）的表达。
SPRC 降低了 AST（ < 0.05）和 ALT（ < 0.01）水平，并减少了炎症细胞因子的释放。机制上，SPRC 增加了 HS 水平（ < 0.05）并促进了胱硫醚 γ-裂解酶（CSE）的表达（ < 0.05）。SPRC 抑制了 MAPK 途径的激活和凋亡途径。SPRC 的所有作用均被 CSE 抑制剂 PAG 阻断。
SPRC 通过促进 CSE 表达和产生内源性 HS 来预防 Con A 诱导的小鼠肝损伤。其机制包括减少炎症细胞因子的释放、减弱 MAPK 途径的激活和减轻凋亡。
