Study on the Mechanism of Shenjing Guben Prescription Regulating PI3K and NRF2 Signaling Pathway in the Treatment of Immune Infertility

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.