[Cerebellar ferroptosis of hypertension mice following lead exposure]

Exploring the changes in cerebellar ferroptosis in hypertensive mice after lead exposure.

Twenty-five healthy C57 male mice were selected to construct a hypertensive model by intraperitoneal injection of angiotensin II(Ang II) at a concentration of 0.05 mg/kg for 7 consecutive days. After a systolic blood pressure of 140 mmHg, 20 hypertensive mice were randomly divided into a hypertensive control group and a hypertensive lead exposure group. Twenty C57 mice with normal blood pressure were randomly divided into a blood pressure normal control group and a blood pressure normal lead exposure group. The mice in the normal blood pressure control group and the hypertensive control group drank water freely. Mice in the lead exposure group with normal blood pressure and the lead exposure group with hypertension drank lead acetate water containing 250 mg/L. Ang II was injected intraperitoneally every two days in the hypertensive control group and hypertensive lead exposed group mice. Each group of mice was poisoned for 12 weeks. Using open field experiments and balance beam experiments to detect motor dysfunction in mice. Using a reagent kit to detect the levels of divalent iron(Fe~(2+)), malondialdehyde(MDA), and glutathione(GSH) in the cerebellum of different groups of mice. Western blot was used to determine the protein expression of member 11 of the solute carrier family 7(SLC7A11), glutathione peroxidase 4(GPX4), nuclear receptor coactivator 4(NCOA4), microtubule associated protein 1 light chain 3B(LC3B), and ferritin heavy chain 1(FTH1) in mouse cerebellar tissue.

The result of the open field experiment showed that the activity distance(1013.04 cm) of mice in the hypertensive lead exposure group was significantly lower than that of the hypertensive control group(1351.18 cm) and the lead exposure group with normal blood pressure(1287.35 cm). And the lead exposure group with hypertension also extended the time through the balance beam, which was 29.40 seconds(P<0.05). In addition, the Fe~(2+)content in the cerebellum of mice in the hypertensive lead exposure group was 3.33 μmol/g prot, which was 1.54 times that of the hypertensive control group and 1.14 times that of the lead exposure group with normal blood pressure. The MDA content was 4.71 nmol/mg prot, higher than that of the hypertensive control group and the lead exposure group with normal blood pressure. The GSH content was 5.36 μmol/g prot, lower than that of the hypertensive control group and the lead exposure group with normal blood pressure(P<0.05). Western blot result showed that compared with the hypertensive control group and the lead exposure group with normal blood pressure, the protein expression of SLC7A11 and GPX4 in the hypertensive lead exposure group was significantly reduced(P<0.05). In addition, compared with the control group with normal blood pressure, the expression of NCOA4 and LC3B proteins in the cerebellum of mice in the hypertension control group and lead exposure group with normal blood pressure increased, while the expression of FTH1 protein decreased(P<0.05). The expression of NCOA4 and LC3B proteins in the hypertensive lead exposure group was higher than that in the hypertensive control group and the lead exposure group with normal blood pressure, while the expression of FTH1 protein decreased(P<0.05).

Lead exposure can exacerbate iron death in the cerebellar tissue of hypertensive mice, and iron autophagy may be involved in its occurrence and development.