Alleviative effect of ginsenoside Rg1 on brain injury induced by chronic intermittent hypoxia in mice and its mechanism
10.13481/j.1671-587X.20240502
- VernacularTitle:人参皂苷Rg1对小鼠慢性间歇性缺氧诱导脑损伤的减轻作用及其机制
- Author:
Yan MENG
1
;
Hongxin WANG
;
Yuhong YANG
Author Information
1. 锦州医科大学药学院药学实验教学中心,辽宁锦州 121001
- Keywords:
Ginsenoside Rg1;
Calpain-1;
Calpain-1 inhibitor;
Chronic intermittent hypoxia;
Brain injury
- From:
Journal of Jilin University(Medicine Edition)
2024;50(5):1196-1204
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To discuss the alleviative effect of ginsenoside Rg1 on chronic intermittent hypoxia(CIH)-induced brain injury in the mice,and to clarify its possible mechanism.Methods:Forty male C57BL/6 mice were randomly divided into control group,model group,inhibitor group(treated with calpain-1 inhibitor),low dose of ginsenoside Rg1 group(treated with 10 mg·kg-1 ginsenoside Rg1),and high dose of ginsenoside Rg1 group(treated with 20 mg·kg-1 ginsenoside Rg1).Except for the control group,the mice in all other groups were placed in a hypoxic chamber with automatically regulated oxygen concentration to induce hypoxic brain injury.The peripheral blood oxygen saturation(SpO2)of tail of the mice in various groups was detected;the escape latencies and path lengths and the frequency of swimming route crossing the target quadrant of the mice in various groups were determined by Morris water maze test;the levels of blood urea nitrogen(BUN),lactate(LA),malondialdehyde(MDA),interleukin-6(IL-6),and tumor necrosis factor-α(TNF-α)and the activities of superoxide dismutase(SOD)and lactate dehydrogenase(LDH)in serum of the mice in various groups were detected by kits;the degrees of brain tissue injury of the mice in various groups were observed by HE staining.The levels of reactive oxygen species(ROS)in CA1 region of hippocampus tissue of the mice in various groups were detected by dihydroethidium(DHE)probe;the expression levels of calpain-1,IL-6,and TNF-α proteins in brain tissue of the mice in various groups were detected by Western blotting method.Results:Compared with control group,the SpO2 of the mice in model group was significantly decreased(P＜0.01),indicating that the model was successfully established.Compared with model group,the SpO2 of the mice in inhibitor group,low dose of ginsenoside Rg1 group and high dose of ginsenoside Rg1 group were significantly increased(P＜0.01).The Morris water maze test results showed that compared with control group,the escape latency and path length of the mice in model group were significantly prolonged(P＜0.01),and the frequency of swimming route of crossing the target quadrant was significantly decreased;compared with model group,the escape latencies and path lengths of the mice in inhibitor group,low dose of ginsenoside Rg1 group and high dose of ginsenoside Rg1 group were significantly shortened(P＜0.01),and the frequency of swimming route of crossing the target quadrant was significantly increased.Compared with control group,the levels of BUN,LA,MDA,IL-6,and TNF-α in serum of the mice in model group were significantly increased(P＜0.01),while the activity of LDH was significantly increased(P＜0.01),and the activity of SOD was significantly decreased(P＜0.01);compared with model group,the levels of BUN,LA,MDA,IL-6,and TNF-α in serum of the mice in inhibitor group,low dose of ginsenoside Rg1 group and high dose of ginsenoside Rg1 group were significantly decreased(P＜0.01),while the activities of LDH were significantly decreased(P＜0.01),and the activities of SOD were significantly increased(P＜0.01).The HE staining results showed that compared with control group,the pyramidal neurons in CA1 region of hippocampus tissue of the mice in model group were loosely arranged,while some neurons were triangular,with nuclear pyknosis,cytoplasmic hyperchromasia,and a few neurons were lost,indicating obvious hypoxic neuronal injury;compared with model group,the hypoxic neuronal injury in CA1 region in hippocampus tissue of the mice in inhibitor group,low dose of ginsenoside Rg1 group and high dose of ginsenoside Rg1 group was effectively alleviated.The DHE probe detection showed that compared with control group,the level of ROS in CA1 region in hippocampus tissue of the mice in model group was significantly increased(P＜0.01);compared with model group,the levels of ROS in CA1 region in hippocampus tissue of the mice in inhibitor group,low dose of ginsenoside Rg1 group and high dose of ginsenoside Rg1 group were significantly decreased(P＜0.01).The Western blotting results showed that compared with control group,the expression levels of calpain-1,TNF-α,and IL-6 proteins in hippocampus tissue of the mice in model group were significantly increased(P＜0.01);compared with model group,the expression levels of calpain-1,TNF-α,and IL-6 proteins in hippocampus tissue of the mice in inhibitor group,low dose of GRg1 group and high dose of GRg1 group were significantly decreased(P＜0.01).Conclusion:Ginsenoside Rg1 can alleviate brain tissue injury of the mice induced by CIH;its mechanism may be related to the inhibition of brain tissue inflammatory response and oxidative stress,and the downregulation of calpain-1 expression.
