Study on the mechanism of Lycium barbarum polysaccharide on reproductive toxicity induced by sevoflurane anesthesia in male rats based on ERK/Nrf2-ARE pathway
10.3760/cma.j.cn101441-20220317-00116
- VernacularTitle:基于ERK/Nrf2-ARE通路探究枸杞多糖对七氟烷麻醉诱导雄性大鼠生殖毒性的拮抗作用机制
- Author:
Ying SUN
1
;
Zhuang LIU
;
Xuenan WANG
Author Information
1. 济宁医学院附属医院麻醉科，济宁 272002
- Publication Type:Journal Article
- Keywords:
Lycium barbarum polysaccharide;
Sevoflurane;
Anesthesia induction;
Reproductive toxicity;
Testis;
Apoptosis
- From:
Chinese Journal of Reproduction and Contraception
2023;43(8):806-812
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the effect of Lycium barbarum polysaccharide (LBP) on sevoflurane anesthesia-induced reproductive toxicity in male rats, and to analyze its effect on extracellular signal-regulated kinase (ERK)/nuclear factor E2-related factor 2 (Nrf2)-antioxidant response element (ARE) signaling pathway.Methods:SD male rats were randomly divided into blank control group, model group, low-dose LBP group, high-dose LBP group and positive control group. Except for the blank control group, the rest were induced by sevoflurane anesthesia and administered by intraperitoneal injection at the same time. The model group was given equal volume of normal saline; the LBP low- and high-dose groups were given 100 mg/kg and 200 mg/kg LBP, once a day, respectively. The positive control group was given 10 mg/kg vitamin E, once every other day. After 14 d of the experiment, all rats were sacrificed. The organ indexes of testis and epididymis of rats in each group were calculated. The contents of testis tissue marker enzymes acid phosphatase (ACP), alkaline phosphatase (AKP) and lactate dehydrogenase (LDH) were detected. HE staining was used to observe the testicular tissue disease of rats. The contents of superoxide dismutase (SOD) and malondialdehyde (MDA) in testis tissue were detected. TUNEL staining was used to observe the apoptosis rate of rat testis tissue. Western blotting was used to detect Bax, Bcl-2 and ERK/Nrf2-ARE pathway protein expression level.Results:In the low-dose and high-dose LBP groups and positive control group, the testicles [(0.39±0.04)%, (0.47±0.05)%, (0.62±0.05)%] and epididymal organ index [(0.08±0.01)%, (0.11±0.01)%, (0.14±0.02)%] were higher than those of the model group [(0.33±0.03)%, (0.05±0.01)%, all P<0.001], ACP [(122.13±5.39) U/g, (115.37±4.45) U/g, (109.74±4.73) U/g] and LDH content [(260.43±15.18) U/g, (245.17±8.13) U/g, (236.19±10.23) U/g] were lower than those in the model group [(129.98±6.17) U/g, (279.89±18.41) U/g, all P<0.001], the AKP content [(224.41±11.69) U/g, (247.59±12.17) U/g, (266.74±13.78) U/g] and SOD activity [(3.11±0.12) U·mg/protein, (4.05±0.14) U·mg/protein, (4.78±0.15) U·mg/protein] were higher than those in the model group [(200.48±10.48) U/g, (2.02±0.09) U·mg/protein, all P<0.001], MDA content [(14.86±1.41) nmol·mg/protein, (10.39±1.22) nmol·mg/protein, (5.25±0.47) nmol·mg/protein] was lower than that in the model group [(18.36±1.99) nmol·mg/protein, all P<0.001], the apoptosis rate of testicular cells was relatively low (all P<0.001) and showed a LBP dose-dependent relationship (all P<0.001). The seminiferous tubule of the model group became thinner, and spermatid were significantly reduced, and only a small amount of spermatogonium remained in some seminiferous tubules. After administration, the structure of seminiferous tubule in the low- and high-dose LBP groups and the positive control group was relatively complete, and spermatid at all levels were arranged in order, the number increased, and vacuoles decreased. The levels of Bcl-2, p-ERK1/2, Nrf2, HO-1, and NQO1 proteins in the testicular tissue of the model group were higher than those of the blank control group, while the levels of Bax protein were lower than those of the blank control group (all P<0.05), the protein levels of Bcl-2, p-ERK1/2, Nrf2, HO-1, and NQO1 in the low- and high-dose LBP groups were higher than those in the model group, while the protein levels of Bax were lower than that in the model group (all P<0.05), and showed a LBP dose-dependent (all P<0.05). Conclusion:LBP has an antagonistic effect on sevoflurane anesthesia-induced reproductive toxicity in male rats, which may be related to the inhibition of ERK/Nrf2-ARE pathway.
