Gui-Ying Zhu,* Dan-Dan Jia,* Ying Yang, Ye Miao, Chao Wang, Chang-Miao Wang Department of General Surgery of Integrated Traditional Chinese and Western Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian, 116011, People’s Republic of China*These authors contributed equally to this workCorrespondence: Chang-Miao WangDepartment of General Surgery of Integrated Traditional Chinese and Western Medicine, The First Affiliated Hospital of Dalian Medical University, No. 222 Zhongshan Road, Xigang District, Dalian City, Liaoning Province, 116011, People’s Republic of ChinaTel +411-83635963-3145Fax +411-83635963Email drwangcm35@outlook.comObjective: This study observes the morphological changes in the enteric nervous system (ENS) – interstitial cells of Cajal (ICC) – smooth muscle cells (SMC) network in sphincter of Oddi dysfunction (SOD) in hypercholesterolemic rabbits following treatment with Shaoyao Gancao decoction (SGD), as well as the apoptosis of the ICC.Methods: In this study, 48 healthy adult New Zealand rabbits are randomly divided into three groups (n = 16 in each group): the control, the model, and the SGD treatment groups. The hypercholesterolemic rabbit model is established. Hematoxylin and eosin staining, transmission electron microscopy, immunofluorescence, terminal deoxynucleotidyl transferase dUTP nick end labeling staining, immunohistochemistry, Western blot analysis, and reverse transcription-polymerase chain reaction are used to detect the morphological changes in the ENS–ICC–SMC network, the expression of apoptosis-related proteins in the ICC, and to observe the curative effect of SGD after treatment.Results: Compared with the control group, the morphology and the ultrastructure of the SO are destroyed in the model group. In addition, the protein gene product 9.5 (PGP9.5), nitric oxide (NO), the SMCs, and the ICC all significantly decreased while substance P (SP) significantly increased. Compared with the model group, the SO morphology and ultrastructure are repaired in the SGD group. In addition, the PGP9.5, NO, the SMCs, and the ICC significantly increased while SP decreased. In addition, SGD may activate the stem cell factor (SCF)/c-Kit signaling pathway to treat SO dysfunction by up-regulating the expression of c-Kit and SCF. Similarly, this pathway restores SO by up-regulating the expression of Bcl2 and inhibiting cleaved caspase-3, Bax, and the tumor necrosis factor.Conclusion: Shaoyao Gancao decoction can promote the recovery of sphincter of Oddi dysfunction in hypercholesterolemic rabbits by protecting the ENS–ICC–SMC network.Keywords: sphincter of Oddi dysfunction, Shaoyao Gancao Decoction, ENS–ICC–SMC, apoptosis
