探讨川芎嗪（TMP）通过SLC7A11/GPX4信号轴调控铁死亡，缓解CCl₄诱导小鼠肝纤维化的作用机制。

将30只C57BL/6雄性小鼠随机分为对照组、CCl₄模型组及TMP低、中、高剂量组（50、100、150 mg/kg）。除对照组外，其余小鼠腹腔注射CCl₄与橄榄油混合液（1 : 10，5 mL/kg），每周2次，持续8周。自第5周起，TMP组小鼠每日灌胃相应剂量TMP，持续4周。检测血清ALT、AST评估肝功能，HE、Masson及天狼星红染色观察病理变化，免疫组化及Western blot检测α-SMA、COL1A1、Fibronectin、SLC7A11、GPX4表达，RT-qPCR检测其mRNA水平，试剂盒检测Fe²⁺、MDA、SOD、GSH水平。多组间比较采用单因素方差分析，组间两两比较采用Tukey事后检验；若数据不符合正态分布或方差齐性，采用Kruskal-Wallis H检验，组间两两比较采用Dunn检验。

与模型组相比，TMP高剂量组ALT水平[（251.70 ± 10.80）比（450.00 ± 14.49）U/L]、AST水平[（236.70 ± 10.80）比（427.50 ± 12.14）U/L]降低，肝组织胶原纤维沉积程度[Masson（1.10 ± 0.07）%比（1.72 ± 0.17）%、Sirius Red （0.17 ± 0.02）%比（0.45 ± 0.04）%]降低，α-SMA蛋白（1.17 ± 0.27比8.08 ± 0.48）、COL1A1蛋白（4.30 ± 0.73比18.78 ± 0.93）、Fibronectin蛋白水平（1.60 ± 0.32比7.75 ± 0.60）降低，SLC7A11蛋白（0.98 ± 0.05比0.29 ± 0.02）、GPX4蛋白水平（0.73 ± 0.08比0.14 ± 0.03）升高，Fe²⁺含量[（2.60 ± 0.14）比（3.63 ± 0.19） μmol/g protein]和MDA含量[（0.72 ± 0.03）比（1.12 ± 0.07） nmol/mg protein]降低，而SOD活性[（1 413.00 ± 47.19）比（1 147.00 ± 42.74）U/mg protein]和GSH含量[（1.60 ± 0.07）比（1.15 ± 0.07） μmol/g protein]升高；SLC7A11 mRNA （0.80 ± 0.07比0.10 ± 0.03）和Gpx4 mRNA水平（0.75 ± 0.07比0.37 ± 0.05）升高，差异均有统计学意义（P均< 0.05）。

TMP可能通过调控SLC7A11/GPX4信号轴抑制铁死亡，从而缓解CCl₄诱导的小鼠肝纤维化，具有潜在抗纤维化应用价值。

To investigate the mechanism of tetramethylpyrazine (TMP) in alleviating CCl₄-induced liver fibrosis in mice by regulating ferroptosis through the SLC7A11/GPX4 signaling axis.

Thirty male C57BL/6 mice were randomly divided into control group, CCl₄ model group, and low-, medium-, high-dose TMP groups (50, 100, and 150 mg/kg). Except for the control group, mice were intraperitoneally injected with a mixture of CCl₄ and olive oil (1 : 10, 5 mL/kg) twice weekly for 8 weeks. From week 5, mice in the TMP groups were administered TMP by gavage once daily for 4 weeks. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were measured to evaluate liver function. Histopathological changes were assessed by hematoxylin-eosin (HE), Masson's trichrome, and Sirius red staining. The expression of α-SMA, COL1A1, Fibronectin, SLC7A11, and GPX4 was detected by immunohistochemistry and Western blot, and their mRNA levels were determined by qPCR. Fe²⁺, malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione (GSH) levels were measured using commercial assay kits. One-way analysis of variance (ANOVA) was used for comparison among multiple groups, and Tukey's post-hoc test was used for pairwise comparison between groups. If the data did not conform to normal distribution or homogeneity of variance, Kruskal-Wallis H test was adopted, and Dunn's test was used for pairwise comparison between groups.

Compared with the model group, the levels of ALT [(251.70 ± 10.80) vs (450.00 ± 14.49) U/L] and AST [(236.70 ± 10.80) vs (427.50 ± 12.14) U/L], the degree of collagen fiber deposition in liver tissue [Masson: (1.10 ± 0.07)% vs (1.72 ± 0.17) %, Sirius Red: (0.17 ± 0.02) % vs (0.45 ± 0.04) %], the protein levels of α-SMA (1.17 ± 0.27 vs 8.08 ± 0.48), COL1A1 (4.30 ± 0.73 vs 18.78 ± 0.93) and Fibronectin (1.60 ± 0.32 vs 7.75 ± 0.60), the contents of Fe²⁺ [(2.60 ± 0.14) vs (3.63 ± 0.19) μmol/g protein] and MDA [(0.72 ± 0.03) vs (1.12 ± 0.07) nmol/mg protein] were decreased in the high-dose TMP group, while the protein levels of SLC7A11 (0.98 ± 0.05 vs 0.29 ± 0.03) and GPX4 (0.73 ± 0.08 vs 0.14 ± 0.03), the activity of SOD [(1 413.00 ± 47.19) vs (1 147.00 ± 42.74) U/mg protein] and the content of GSH [(1.60 ± 0.07) vs (1.15 ± 0.07) μmol/g protein], the mRNA levels of SLC7A11 (0.80 ± 0.07 vs 0.10 ± 0.03) and Gpx4 (0.75 ± 0.07 vs 0.37 ± 0.05) were increased, all these differences were statistically significant (all P < 0.05).

TMP may alleviate CCl₄-induced liver fibrosis in mice by regulating the SLC7A11/GPX4 signaling axis to inhibit ferroptosis, which has potential anti-fibrotic application value.