Objective. To explore the mechanism of Shenjing Guben prescription (SP) in the treatment of immune infertility by regulating PI3K-NRF2/p38 signal pathway. Methods. 60 adult male SD rats were randomly divided into control group (NC group), ACN group, low concentration AP intervention group (low group), middle concentration SP intervention group (middle group), and high concentration SP intervention group (high group). 12 rats in each group were administered by gavage once a day, 6 days/w, and the rats were killed after 28 days. Bilateral testis and epididymis were removed and weighed and organ coefficients were calculated, and testicular histopathological sections were prepared to evaluate the changes of testicular tissue structure. The relative expression levels of PI3K, MKK7, JNK, p38 mRNA, and protein in testis were measured by QRT-PCR and western blot. Results. (1) Compared with the control group, the proportion of grade A and B sperms in ACN group increased significantly, and the proportion of grade D sperm decreased significantly ( P < 0.05). After SP intervention, compared with ACN group, there was no significant difference in the proportion of sperm at all levels in low, medium, and high SP intervention groups ( P > 0.05). (2) Compared with the control group, the sperm VCL, VSL, VAP, and mad in ACN group increased significantly, and the BCF decreased significantly ( P < 0.05). After SP intervention, compared with ACN group, there was no significant difference in sperm motility parameters among low, medium, and high SP intervention groups ( P > 0.05). (3) Compared with the control group, the activities of AKP and SDH in testicular tissue of rats in ACN group decreased significantly ( P < 0.05). After SP intervention, compared with ACN group, AKP activity increased significantly and LDH activity decreased significantly in low, medium, and high SP intervention groups ( P < 0.05). (4) Compared with the control group, the expression levels of PI3K, p-PI3K, MKK7, p-MKK7, JNK, p-JNK, p38, and p-p38 proteins and the ratios of p-JNK/JNK and p-p38/p38 increased in the testis of ACN group ( P < 0.05). After SP intervention, compared with ACN group, the protein expression levels of PI3K, p-PI3K, MKK7, p-MKK7, JNK, p-JNK, p38, and p-p38 in testicular tissue of SP intervention group decreased, and the ratio of p-JNK/JNK and p-p38/p38 decreased ( P < 0.05). Conclusion. SP can reduce the oxidative stress of testis induced by ACN and inhibit the activation of PI3K-NRF2/p38 signal pathway.
Background: Infertility is an important social problem. Asthenozoospermia (AZS) is a common pathological cause of male infertility, but its pathogenesis is unclear. Shenjing Guben Wan (SJGBW), a traditional Chinese medicine, has shown remarkable effects during the clinical treatment of oligozoospermia or AZS.Methods: In this study, clinical evaluations were carried out on 184 AZS patients receiving SJGBW treatment, including sperm count, sperm quality, and pregnancy rate. Also, ornidazole was used to build an AZS mouse model, and SJGBW treatment was administered. The sperm quantity and fertility of mice in different groups were evaluated; a cholecystokinin octapeptide-8 (CCK-8) experiment was carried out to test the activity of seminiferous epithelium Sertoli cells, and immunohistochemistry and the Terminal Deoxynucleotidyl Transferase-mediated dUTP Nick-End Labeling (TUNEL) method were employed to test the pathological information and expression of the Sertoli cell surface marker in the testicular tissues of mice in each group. Results:The sperm vitality, progressive sperm motility, and sperm morphology of patients who received SJGBW treatment were all improved (P<0.05). In the AZS group, the average sperm count, sperm vitality, pregnancy rate, and female mouse litters were all lower relative to mice in the control group. Following SJGBW treatment, the average sperm count, sperm vitality, pregnancy rate, and female mouse litters of mice in the AZS group were all significantly improved. The cytobiological experimental results showed that compared with the serum of normal male mice in the control group, the drug serum containing SJGBW could improve the cell vitality and proliferative ability of seminiferous epithelium Sertoli cells in AZS mice.Furthermore, the TUNEL results showed that the seminiferous tubule Sertoli cells and mesenchymal cells of the AZS mice exhibited the most significant apoptosis, which was alleviated following SJGBW treatment.Moreover, the levels of Sertoli cell marker, SOX9, and anti-apoptosis protein, Bcl2, in SJGBW-treated mice were both higher than that in AZS mice.Conclusions: SJGBW can promote the development and maturation of germ cells by facilitating the proliferation of Sertoli cells in AZS patients, thereby improving the fertility of these patients.
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