Li Caixia, Cui Lihua, Zhang Lanqiu, Yang Lei, Zhuo Yuzhen, Cui Jialin, Cui Naiqiang, Zhang Shukun
Tianjin Key Laboratory of Acute Abdomen Disease Associated Organ Injury and ITCWM Repair, Institute of Acute Abdominal Diseases of Integrated Traditional Chinese and Western Medicine, Tianjin Nankai Hospital, Nankai Clinical College, Tianjin Medical University, Tianjin, China.
The Clinical Medicine, Tianjin Medical University, Tianjin, China.
Front Pharmacol. 2021 Oct 21;12:735079. doi: 10.3389/fphar.2021.735079. eCollection 2021.
Chronic pancreatitis (CP) is a progressive fibro-inflammatory syndrome. The damage of acinar cells is the main cause of inflammation and the activation of pancreatic stellate cells (PSCs), which can thereby possibly further aggravate the apoptosis of more acinar cells. Saikosaponind (SSd), a major active ingredient derived from Chinese medicinal herb bupleurum falcatum, which exerted multiple pharmacological effects. However, it is not clear whether SSd protects pancreatic injury of CP via regulating the apoptosis of pancreatic acinar cells. This study systematically investigated the effect of SSd on pancreatic injury of CP and . The results revealed that SSd attenuate pancreatic damage, decrease the apoptosis and suppress the phosphorylation level of MAPK family proteins (JNK1/2, ERK1/2, and p38 MAPK) significantly in the pancreas of CP rats. In addition, SSd markedly reduced the apoptosis and inflammation of pancreatic acinar AR42J cells induced by cerulein, a drug induced CP, or Conditioned Medium from PSCs (PSCs-CM) or the combination of PSCs-CM and cerulein. Moreover, SSd significantly inhibited the activated phosphorylation of JNK1/2, ERK1/2, and p38 MAPK induced by cerulein or the combination of PSCs-CM and cerulein in AR42J cells. Furthermore, SSd treatment markedly decreased the protein levels of p-JNK and p-p38 MAPK caused by PSCs-CM alone. In conclusion, SSd ameliorated pancreatic injury, suppressed AR42J inflammation and apoptosis induced by cerulein, interrupted the effect of PSCs-CM on AR42J cells inflammation and apoptosis, possibly through MAPK pathway.
慢性胰腺炎（CP）是一种进行性纤维炎症综合征。腺泡细胞损伤是炎症和胰腺星状细胞（PSC）激活的主要原因，这可能会进一步加重更多腺泡细胞的凋亡。柴胡皂苷d（SSd）是中药柴胡的主要活性成分，具有多种药理作用。然而，尚不清楚SSd是否通过调节胰腺腺泡细胞凋亡来保护CP的胰腺损伤。本研究系统地研究了SSd对CP胰腺损伤的影响。结果显示，SSd可减轻CP大鼠胰腺损伤，显著降低胰腺细胞凋亡，并抑制MAPK家族蛋白（JNK1/2、ERK1/2和p38 MAPK）的磷酸化水平。此外，SSd显著降低了由雨蛙素（一种诱导CP的药物）、PSC条件培养基（PSCs-CM）或PSCs-CM与雨蛙素联合诱导的胰腺腺泡AR42J细胞的凋亡和炎症。此外，SSd显著抑制了雨蛙素或PSCs-CM与雨蛙素联合诱导的AR42J细胞中JNK1/2、ERK1/2和p38 MAPK的激活磷酸化。此外，SSd处理显著降低了单独PSCs-CM引起的p-JNK和p-p38 MAPK蛋白水平。总之，SSd改善了胰腺损伤，抑制了雨蛙素诱导的AR42J炎症和凋亡，中断了PSCs-CM对AR42J细胞炎症和凋亡的影响，可能是通过MAPK途径实现的。
