关键词: 神经痛, 带状疱疹后, 带状疱疹, 土鳖虫, 线粒体自噬, 细胞因子类, 神经肽类, 金边土鳖多肽

Abstract: 【Abstract】 Objective To investigate the analgesic effect of Opisthoplatia orientalis Burm. polypeptides （OOBP） on postherpetic neuralgia （PHN） induced by resiniferatoxin （RTX） in rat models, and its effect on the phosphatase and tensin homologue deleted on chromosome ten （PTEN）-induced kinase 1/Parkin （PINK1/Parkin） signaling pathway. Methods Thirty-two special pathogen-free rats were randomly divided into 2 groups: a blank control group （n = 8） receiving intraperitoneal injections of physiological saline （0.20 mg/kg）, and a model group （n = 24） receiving intraperitoneal injections of RTX （0.20 mg/kg） to establish the PHN rat model. The rats' paw withdrawal mechanical threshold （PWMT） was measured on days 1, 4, 7, and 10 after RTX injections. After 10 days of RTX treatment, rat models were randomly assigned to 3 subgroups: PHN group, OOBP group, and gabapentin group, with 8 rats in each group. The OOBP group and gabapentin group were gavaged with OOBP （equivalent to 0.9 g raw drug per kg） and gabapentin （27 mg/kg） respectively, while the PHN group and control group were gavaged with physiological saline. All treatments lasted for 3 weeks, during which PWMT was continuously monitored. One hour after the final dose, rats were sacrificed, and spinal cord tissues and serum samples were collected. Hematoxylin-eosin （HE） staining was performed to observe spinal pathological changes, enzyme-linked immunosorbent assay （ELISA） to detect serum levels of interleukin-10 （IL-10）, tumor necrosis factor-α （TNF-α）, β-endorphin （β-EP）, and calcitonin gene-related peptide （CGRP）, and Western blot analysis to determine the expression of PINK1, Parkin, and ubiquitin-binding protein P62 in rat spinal cord tissues. The entropy weight method was applied to comprehensively evaluate the effect of OOBP on the above cytokines, proteins and other pharmacodynamic indicators in rat models of PHN. Results From day 1 to day 10 after modeling, PWMT values in the model group were significantly lower than those in the blank control group （all P < 0.05）, and also significantly lower than baseline values prior to modeling （all P < 0.05）. Histopathological analysis of rat spinal cord tissues showed less pathological changes （such as Nissl body swelling and neuronal necrosis） but more normal Nissl bodies in both the gabapentin group and OOBP group compared with the PHN group. ELISA revealed significantly decreased serum levels of TNF-α and CGRP but significantly increased serum levels of β-EP and IL-10 in the OOBP group compared with the PHN group （all P < 0.05）. Western blot analysis showed that expression levels of PINK1 and Parkin were significantly lower in the gabapentin group （0.441 ± 0.061, 0.597 ± 0.180, respectively） and the OOBP group （0.666 ± 0.117, 0.481 ± 0.073, respectively） than in the PHN group （1.033 ± 0.085, 1.088 ± 0.040, respectively, all P < 0.05）; in contrast, the P62 expression significantly increased in the gabapentin group （0.810 ± 0.086） and OOBP group （0.902 ± 0.153） compared with the PHN group （0.543 ± 0.082, both P < 0.05）. The entropy weight analysis showed that the comprehensive scores were 0.222 and 0.229 in the OOBP group and the gabapentin group respectively, suggesting a greater overall therapeutic effect of OOBP. Conclusion OOBP may exert analgesic effects in rat models of PHN by downregulating the expression of inflammatory factors and pain-related factors and modulating the PINK1/Parkin signaling pathway, thereby inhibiting mitochondrial autophagy in spinal neurons and reducing inflammatory responses.

Key words: Neuralgia, postherpetic, Herpes zoster, Eupolyphaga steleophaga, Mitophagy, Cytokines, Neuropeptides, Opisthoplatia orientalis Burm. polypeptides