PI3K/Akt信号通路在虾青素调节LX-2细胞活化中作用

Role of PI3K/Akt signaling pathway in moderating effect of astaxanthin on activation of LX-2 cells

目的探讨磷脂酰肌醇3-激酶/蛋白激酶B(PI3K/Akt)信号通路在虾青素调节人肝星状细胞(LX-2细胞)活化中的作用。方法实验设对照组、低、中、高剂量虾青素组(5、10、20μmol/L)、抑制剂组(25μmol/L LY294002)、抑制剂+虾青素组(25μmol/L LY294002+20μmol/L虾青素),作用48 h后检测LX-2细胞中α-平滑肌肌动蛋白(α-SMA)和Ⅰ型胶原(col1a1)mRNA表达水平、各组细胞Akt及其磷酸化水平。结果与对照组比较,虾青素组LX-2细胞中α-SMA和col1a1 mRNA表达明显降低,并呈剂量依赖关系(P<0.05);与对照组比较,抑制剂组LX-2细胞中磷酸化Akt水平(0.42±0.05)、α-SMA和col1a1 mRNA表达水平[分别为(0.23±0.05)、(0.35±0.06)]均明显降低(P<0.05);与对照组比较,虾青素组LX-2细胞中磷酸化Akt水平(0.60±0.07)、α-SM A和col1a1 mRNA表达水平[分别为(0.48±0.07)、(0.61±0.04)]均明显降低(P<0.05);与抑制剂组比较,抑制剂+虾青素组LX-2细胞中磷酸化Akt水平(0.18±0.04)、α-SMA和col1a1 mRNA表达水平[分别为(0.11±0.05)、(0.20±0.03)]均明显降低(P<0.05)。结论虾青素可通过PI3K/Akt信号通路抑制肝星状细胞活化,发挥抗非酒精性脂肪肝纤维化作用。

Objective To investigate the role of phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt） signa- ling pathway in moderating effect of astaxanthin on the activation of human hepatic stellate cells （ LX-2 cell）. Methods LX-2 cells were divided into a control group, three astaxanthin groups at the dosages of 5,10, and 20μmol/L, and in- hibitor group （25 μmol/L LY294002）, and an inhibitor plus astaxanthin group （25μmol/L LY294002 and 20 μmol/L astaxanthin）. The mRNA expressions of a-smooth muscle actin （α-SMA） and collagen I （coil al ）, and protein expres- sion of Akt,phosphorylated Akt （p-Akt） in LX-2 cells were detected 48 hours after the treatments. Results The mRNA expressions of tx-SMA and collal in LX-2 cells of astaxanthin groups were obviously decreased in a dose-response manner compared with those of the control group （both P 〈 0. 05 ）. The protein expression of p-Akt （0. 42 ±0.05 ） and mRNA expressions of α-SMA （0. 23 ±. 05） and collal （0. 35 ±. 06） in LX-2 cells of inhibitor group were obviously reduced compared to those of the control group （ all P 〈 0. 05 ） ; the protein expression of p-Akt （ 0. 60 ± 0.07 ） and mRNA expressions of α-SMA （0. 48 ±0. 07 ）and coil al （0. 61 ±0. 04） in LX-2 cells of astaxanthin groups were obvi- ously decreased compared to those of the control group （ all P 〈 0. 05 ） ; the protein expression of p-Akt （0. 18 ±0. 04） and mRNA expressions of α-SMA （0. 11 ± 0. 05 ） and coil al （0. 20 ±0. 03 ） in LX-2 cells of inhibitor plus astaxanthin group were obviously reduced compared with those of the inhibitor group （ all P 〈 0. 05 ）. Conclusion Astaxanthin can restrain the activation of hepatic stellate cells through the PI3K/Akt signaling pathway and play an important role in inhibiting the occurrence of fibrosis in non-alcoholic fatty liver disease.