Rutaecarpine may improve neuronal injury, inhibits apoptosis, inflammation and oxidative stress by regulating the expression of ERK1/2 and Nrf2/HO-1 pathway in rats with cerebral ischemia-reperfusion injury

Figures & data

Figure 1 Rut relieves neurological damage in a MCAO rat model. The rats were grouped into five groups (ten in each group): control group, the rats were received similar surgical treatment but no screws were inserted; CI/R model; CI/R+Rut (5 mg/kg), the CI/R rats were treated with 5 mg/kg for 4 weeks; CI/R+Rut (10 mg/kg), the CI/R rats were treated with 10 mg/kg for 4 weeks; CI/R+Rut (20 mg/kg), the CI/R rats were treated with 20 mg/kg for 4 weeks. (A) Neurologic function score. (B) Neuronal injury was detected by HE staining. (*p<0.05 vs control group; #p<0.05 vs CI/R group).

Abbreviations: CI/R, cerebral ischemia-reperfusion; Rut, rutaecarpine; MCAO, middle cerebral artery occlusion.

Figure 2 Rut inhibits the apoptosis of nerve cells in MCAO rats. The rats were grouped into five groups (ten in each group): control group, the rats were received similar surgical treatment but no screws were inserted; CI/R model; CI/R+Rut (5 mg/kg), the CI/R rats were treated with 5 mg/kg for 4 weeks; CI/R+Rut (10 mg/kg), the CI/R rats were treated with 10 mg/kg for 4 weeks; CI/R+Rut (20 mg/kg), the CI/R rats were treated with 20 mg/kg for 4 weeks. (A) Apoptotic cells were measured by TUNEL staining. (B) The mRNA and protein levels of caspase 3 were measured by RT-qPCR and Western blotting. (C) The protein levels of Bcl-2 and Bax were measured by Western blotting. GAPDH was used as the internal reference. (*p<0.05 vs control group; #p<0.05 vs CI/R group).

Abbreviations: CI/R, cerebral ischemia-reperfusion; Rut, rutaecarpine; MCAO, middle cerebral artery occlusion; TUNEL, terminal deoxynucleotidyl transferase dUTP nick end labeling.

Figure 3 Rut regulates inflammatory response in MCAO rats. The rats were grouped into five groups (ten in each group): Control group, the rats were received similar surgical treatment but no screws were inserted; CI/R model; CI/R+Rut (5 mg/kg), the CI/R rats were treated with 5 mg/kg for 4 weeks; CI/R+Rut (10 mg/kg), the CI/R rats were treated with 10 mg/kg for 4 weeks; CI/R+Rut (20 mg/kg), the CI/R rats were treated with 20 mg/kg for 4 weeks. (A) The levels of pro-inflammatory factors (IL-6 and IL-1β) were measured by ELISA. (B) The levels of an-inflammatory factors (IL-4 and IL-10) were measured by ELISA. (*p<0.05 vs control group; #p<0.05 vs CI/R group).

Abbreviations: CI/R, cerebral ischemia-reperfusion; Rut, rutaecarpine; MCAO, middle cerebral artery occlusion.

Figure 4 Rut improves oxidative stress in MCAO rats. The rats were grouped into five groups (ten in each group): control group, the rats were received similar surgical treatment but no screws were inserted; CI/R model; CI/R+Rut (5 mg/kg), the CI/R rats were treated with 5 mg/kg for 4 weeks; CI/R+Rut (10 mg/kg), the CI/R rats were treated with 10 mg/kg for 4 weeks; CI/R+Rut (20 mg/kg), the CI/R rats were treated with 20 mg/kg for 4 weeks. (A) SOD. (B) MDA. (C) LDH. (D) ROS. (*p<0.05 vs control group; #p<0.05 vs CI/R group).

Abbreviations: CI/R, cerebral ischemia-reperfusion; Rut, rutaecarpine; MCAO, middle cerebral artery occlusion.

Figure 5 Rut inhibits the ERK pathway and activates the Nrf2 pathway. The rats were grouped into five groups (ten in each group): control group, the rats were received similar surgical treatment but no screws were inserted; CI/R model; CI/R+Rut (5 mg/kg), the CI/R rats were treated with 5 mg/kg for 4 weeks; CI/R+Rut (10 mg/kg), the CI/R rats were treated with 10 mg/kg for 4 weeks; CI/R+Rut (20 mg/kg), the CI/R rats were treated with 20 mg/kg for 4 weeks. (A) The protein levels of ERK1/2 and p-ERK1/2 were measured by Western blotting. (B) The protein levels of Nrf2, HO-1 and NQO1 were measured by Western blotting. Actin was used as the internal reference. (*p<0.05 vs control group; #p<0.05 vs CI/R group).

Abbreviations: ERK, extracellular regulated protein kinase; Nrf2, nuclear factor-erythroid 2 related factor 2; CI/R, cerebral ischemia-reperfusion; Rut, rutaecarpine; HO-1, heme oxygenase 1; NQO1, NAD (P) H-quinone oxidoreductase 1.