peoniflorin and Hypercholesterolemia

Sphincter of Oddi dysfunction (SOD) is a benign obstructive disorder predominantly resulting from spasms of the SO. Pharmacological therapies aim to induce SO relaxation; the hypercholesterolemic (HC) rabbit is the only SOD model available for study. In the present study, SO muscle strips, intracellular calcium ion concentrations and the mRNA expression levels of the α1C subunit of the L‑type calcium channel in the SO muscle cells of HC rabbits were employed to investigate the effects of paeoniflorin (PF). Alterations in L‑type calcium channel α subunit 1C mRNA and protein expression in SO cells with HC following the application of different concentrations of PF were determined by reverse transcription‑quantitative polymerase chain reaction and western blotting. The whole cell patch clamp technique was used to observe the effects of different concentrations of paeoniflorin on L‑type calcium channel current. The results of the present study demonstrated that PF induced the relaxation of SO muscle strips and reduced the intracellular calcium concentration in the SO muscle cells of HC rabbits. In addition, PF decreased the mRNA expression levels of the α1C subunit of the L‑type calcium channel and reduced the L‑type calcium channel current in SO cells. These results suggested that the mechanism underlying the relaxation of the SO muscle by PF may be associated with the reduction of calcium ion influx via L‑type calcium channels.

Topics: Action Potentials; Animals; Anti-Inflammatory Agents, Non-Steroidal; Calcium; Calcium Channels, L-Type; Cholesterol; Disease Models, Animal; Female; Glucosides; Hypercholesterolemia; Male; Monoterpenes; Muscle Tonus; Muscles; Patch-Clamp Techniques; Rabbits; Sphincter of Oddi

This study aimed to investigate the influence of hypercholesterolemia (HC) on intracellular calcium ion concentration in the sphincter of Oddi (SO) of rabbits and the influence of paeoniflorin on intracellular calcium ion concentration in the hypercholesterolemic rabbit SO. Sixteen purebred New Zealand rabbits were randomly divided into two groups: the control group and the HC model group (8 rabbits in each group). The control group was fed standard diet. The HC group was fed standard diet plus cholesterol for a total of 8 weeks to induce and establish the rabbit HC model. The SO segment of HC rabbits was taken and enzyme treated to obtain SO cells. After primary culture, immunohistochemical analysis was performed. Fluo-3/AM was used to load SO cells, and then intracellular calcium ion concentration was determined by confocal microscopy. Intracellular calcium ion in the SO of the HC group was higher than that of the normal group; intracellular calcium ion in the HC rabbit SO of the paeoniflorin group was lower than that of the control group, where the paeoniflorin effect was greater with higher concentrations. High cholesterol caused an increase in intracellular calcium ion concentration in the rabbit SO, and paeoniflorin can reduce intracellular calcium ion concentration in the HC rabbit SO in a concentration-dependent manner.

Topics: Aniline Compounds; Animals; Anti-Inflammatory Agents, Non-Steroidal; Calcium; Cholesterol; Dose-Response Relationship, Drug; Epithelial Cells; Female; Fluorescent Dyes; Glucosides; Hypercholesterolemia; Ion Transport; Male; Monoterpenes; Primary Cell Culture; Rabbits; Sphincter of Oddi; Xanthenes