Influences of urinary kallidinogenase on neuronal apoptosis in cerebral infarction rats through Nrf2/ARE oxidative stress pathway.

Abstract

OBJECTIVE:

To investigate the influences of urinary kallidinogenase on neuronal apoptosis in rats with cerebral infarction through the nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response element (ARE) oxidative stress pathway.

MATERIALS AND METHODS:

A total of 30 male rats were divided into group A (model control group), group B (rat model of cerebral infarction) and group C (rat model of cerebral infarction + medical treatment with urinary kallidinogenase). The percentage of cerebral infarct volume and the apoptosis of brain cells in the three groups of rats were detected via 2,3,5-Triphenyltetrazolium chloride (TTC) staining, the pathological morphology of brain tissues in the three groups of rats was observed via hematoxylin and eosin (HE) staining, and the protein levels of Nrf2 and superoxide dismutase 1 (SOD1) in the brain tissues in the three groups of rats were measured using the Western blotting assay.

RESULTS:

The degree of neurological deficit in group B was remarkably higher than that in group A (p<0.05), and it was markedly decreased in group C compared to that in group B, displaying statistically significant differences (p<0.05). Compared to that in group A, the cell apoptosis was significantly aggravated in group B, while a remarkably alleviated cell apoptosis was observed in group C compared to that of group B, and the differences were statistically significant (p<0.05). The cerebral infarct volume accounted for 34.87% of the whole brain volume in group B, and a mild cerebral infarction was detected in group C, with a percentage of cerebral infarct volume of 21.14%. Group B showed a more evident increase in the cerebral infarct volume than in group C (p<0.05). Compared to those of group A, pyknotic nuclei and neuron staining of brain tissue cells were evidently increased, and the neuronal cell injury was aggravated in group B. Moreover, prominently decreased pyknotic nuclei and neuron staining (p<0.05) as well as mild neuronal cell injury (p<0.05) were detected in group C compared to those in group B. The levels of Nrf2 and SOD1 protein in the brain tissues in group B were remarkably lower than those of group C (p<0.05).

CONCLUSIONS:

Urinary kallidinogenase can inhibit the neuronal apoptosis in rats and protect the rats from cerebral infarction, whose mechanism is associated with the activation of the Nrf2/ARE oxidative stress pathway.

• Authors: Q-Y Fan, Z Qiu, X-D Zhang
• Journal: European review for medical and pharmacological sciences (Eur Rev Med Pharmacol Sci) Vol. 23 Issue 15 Pg. 6665-6671 (Aug 2019) ISSN: 2284-0729 [Electronic] Italy
• PMID: 31378909 (Publication Type: Journal Article)

Chemical References

• NF-E2-Related Factor 2
• Nfe2l2 protein, rat
• Sod1 protein, rat
• Superoxide Dismutase-1
• Kallikreins

Topics

• Animals
• Antioxidant Response Elements (genetics)
• Apoptosis (drug effects, genetics)
• Brain (cytology, drug effects, pathology)
• Brain Infarction (drug therapy, pathology)
• Disease Models, Animal
• Humans
• Injections, Intraperitoneal
• Kallikreins (pharmacology, therapeutic use)
• Male
• NF-E2-Related Factor 2 (metabolism)
• Neurons (drug effects, pathology)
• Oxidative Stress (drug effects, genetics)
• Rats
• Rats, Sprague-Dawley
• Signal Transduction (drug effects, genetics)
• Superoxide Dismutase-1 (metabolism)