Objective

2

To explore the potential mechanism by which the Lidan Xiaoshi Mixture （利胆消石合剂， LXM） can prevent the recurrence of common bile duct stones （CBDS）.

Methods

2

Eighty-five guinea pigs were randomly divided using a random number table， 10 in the control group， and 15 each in the model group， Danning Tablet （胆宁片， DT） group， LXM low-， middle-， and high-dose group. Except for the guinea pigs in the control group which underwent sham surgery， the CBDS models were established by common bile duct intubation and injection of biliary bacterial culture solution from patients with recurrent CBCS. On the day after modeling， the DT group was given DT suspension by gavage at a dose of 0.05 g/（100 g·d）； the LXM low-， middle-， and high-dose groups were administered LXM granules by gavage at doses of 0.16， 0.32， and 0.64 g/（100 g·d） respectively； while the control group and the model group were given 1 ml/（100 g·d） of distilled water by gavage. All groups administrated via gavage for continuous 7 days. Samples were collected on the day after the last gavage to observe the conditions of the common bile duct and gallbladder in guinea pigs. The levels of motilin （MTL）， vasoactive intestinal peptide （VIP）， somatostatin （SS）， and cholecystokinin （CCK） in serums of each group were detected by ELISA； the histopathology changes of the Oddi sphincter and bile duct tissues in each group were observed by HE staining； the number of Cajal-like interstitial cells （ICLC） in the Oddi sphincter and bile duct tissues was detected by immunofluorescence staining； the protein levels of tyrosine kinase receptor （c-kit） and stem cell factor （SCF） in the Oddi sphincter tissues were detected by Western Blot.

Results

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In the model group， yellow flocculent solids were observed in the common bile duct of guinea pigs， and the bile in the gallbladder was turbid with partial stone formation. The increased damage and inflammatory reactions in the Oddi sphincter and bile duct tissues were observed in HE staining. In contrast， in the DT group and all LXM dose groups， the bile in the common bile duct and gallbladder was clear with no obvious precipitation； histopathol

oy results showed no significant biliary tissue damage or inflammatory reaction in the LXM high-dose group. Compared with the control group， the model group exhibited decreased levels of MTL and CCK， increased levels of VIP and SS in serum， reduced number of ICLC in the Oddi sphincter and bile duct tissues， and decreased protein levels of c-kit and SCF in the Oddi sphincter tissue （

P

＜0.05 or

P

＜0.01）. Compared with the model group， all LXM dose groups showed increased levels of MTL and CCK， decreased levels of VIP and SS in serum， an increased number of ICLC in the Oddi sphincter and bile duct tissues， and elevated protein levels of c-kit and SCF in the Oddi sphincter tissue （

P

＜0.05 or

P

＜0.01）. Compared with the DT group， the LXM middle-dose and high-dose groups had increased levels of MTL and CCK and lower levels of SS. The number of ICLC in the Oddi sphincter of the LXM middle-dose group and in the bile duct tissues of all LXM dose groups was increased； the protein levels of c-kit and SCF in the Oddi sphincter tissue of the LXM low-dose and middle-dose groups were elevated （

P

＜0.05 or

P

＜0.01）.

Conclusion

2

LXM may reduce cholestasis and stone formation by alleviating inflammatory reactions in biliary tissues， regulating gastrointestinal hormones， activating the c-kit/SCF signaling pathway， and increasing the number of ICLC， thereby reducing cholestasis and calculus formation， and preventing the recurrence of CBDS.