[Protective Effect of Endogenous ω-3 Polyunsaturated Fatty Acid Against Cisplatin Induced Myelosuppression].

Abstract

Objective: To investigate the protective effect of endogenous ω-3 polyunsaturated fatty acid (PUFA) against cisplatin-induced myelosuppression and the mechanism of reducing apoptosis in bone marrow nucleated cells using mfat-1 transgenic mice.

Methods: The experimental animals were divided into 4 groups: wild-type mice normal control group, mfat-1 transgenic mice normal control group, wild-type mice model group and mfat-1 transgenic mice model group. The mice in the model group were injected intraperitoneally with 7.5 mg/kg cisplatin on day 0 and day 7 to construct a myelosuppression model, while the mice in the normal control group were injected intraperitoneally with an equal amount of saline, and their status was observed and their body weight was measured daily. Peripheral blood was taken after 14 day for routine blood analysis, and the content and proportion of PUFA in peripheral blood were detected using gas chromatography. Bone marrow nucleated cells in the femur of mice were counted. The histopathological changes in bone marrow were observed by histopathological staining. The apoptosis of nucleated cells and the expression level changes of apoptosis-related genes in the bone marrow of mice were detected by flow cytometry and fluorescence quantitative PCR.

Results: Compared with wild-type mice, mfat-1 transgenic mice showed significantly increased levels of ω-3 PUFA in peripheral blood and greater tolerance to cisplatin. Peripheral blood analysis showed that endogenous ω-3 PUFA promoted the recovery of leukocytes, erythrocytes, platelets and haemoglobin in peripheral blood of myelosuppressed mice. The results of HE staining showed that endogenous ω-3 PUFA significantly improved the structural damage of bone marrow tissue induced by cisplatin. Flow cytometry and PCR showed that, compared with wild-type mice model group, the apoptosis rate of bone marrow nucleated cells in mfat-1 transgenic mice was significantly reduced ( P < 0.001), and the expression of anti-apoptotic genes Bcl-2 mRNA was significantly increased ( P < 0.01), while the expressions of pro-apoptotic genes Bax and Bak mRNA were significantly reduced ( P < 0.001, P < 0.05).

Conclusion: Endogenous ω-3 PUFA can reduce cisplatin-induced apoptosis in bone marrow nucleated cells, increase the number of peripheral blood cells and exert a protective effect against cisplatin-induced myelosuppression by regulating the expression of apoptosis-related genes.