ABSTRACT
Slow transit constipation (STC) is a common type of constipation with a high incidence rate and a large number of patients. We aimed to investigate the therapeutic effects and potential mechanism of paeoniflorin (PAE) on loperamide-induced Sprague Dawley (SD) rat constipation models. Rats with loperamide-induced constipation were orally administered different concentrations of PAE (10, 20, or 40 mg/kg). In vitro, enterochromaffin (EC)-like RIN-14B cells were treated with 20, 40, or 80 µg/ml PAE. We found that PAE treatment significantly improved the symptoms of constipation and increased the intestinal transit rate. Hematoxylin and eosin (H&E) staining showed that PAE alleviated colonic tissue pathological damage. Besides, our results implied that PAE concentration-dependently promoted the content of 5-hydroxytryptamine (5-HT) catalyzed by tryptophan hydroxylase (Tph)-1 in the serum of loperamide-induced rats and in RIN-14B cells. Western blot and immunofluorescence (IF) stain indicated that PAE also promoted the expression of G protein-coupled BA receptor 1 (TGR5), transient receptor potential ankyrin 1 (TRPA1), phospholipase C (PLC)-γ1, and phosphatidylinositol 4,5-bisphosphate (PIP2) in vivo and in vitro. RIN-14B cells were cotreated with a TGR5 inhibitor (SBI-115) to explore the mechanism of PAE in regulating the 5-HT secretion. We observed inhibition of TGR5 reversed the increase of 5-HT secretion induced by PAE in RIN-14B cells. We provided evidence that PAE could promote 5-HT release from EC cells and improve constipation by activating the TRPA1 channel and PLC-γ1/PIP2 signaling. Thus, PAE may provide therapeutic effects for patients with STC.
ABSTRACT
OBJECTIVE: To evaluate the preliminary clinical outcomes of percutaneous endoscopic lumbar discectomy (PELD) for patient with upper lumbar disc herniation and failing to respond to conservative treatment. METHODS: From December 2008 to June 2011, 12 patients with upper lumbar disc herniation and failing to respond to conservative treatment were treated, including 8 males and 4 females, aged from 28 to 82 years old (averaged, 50.67 years old). Duration of upper lumbar disc herniation was 3 to 10 months, with an average of 5.75 months. MRI exam revealed 12 "degeneration discs" low in signal on T2 image, including 1 discs of T12L1, 1 of L1,2, 3 of L2,3 and 7 of L3,4. Discography showed positive response, fluoroscopy confirmed annulus fibrosus tears of posterior intervertebral disc in 12 discs. PELD was performed. Visual analogue scale (VAS) and Oswestry disability index (ODI) were evaluated before operation and after operation. The clinical outcome was determined by modified Macnab criteria at the final follow-up. RESULTS: The average operation time of each patient was 1.45 h (ranged, 1.0 to 2.5 h), and the mean length of postoperative hospital stay was 5.83 days (ranged,4 to 9 days). There was no happening in ruptured meninges and nerve damage. Twelve patients were followed up,and the duration ranged from 1 to 12 months (averaged, 5.5 months). The VAS score decreased from preoperative 8.00 +/- 1.21 to postoperative 1.92 +/- 0.79 (P < 0.01). The ODI decreased from preoperative (78.81 +/- 13.65)% to the final follow-up (16.19 +/- 3.52)% (P < 0.01). According to the modified Macnab criteria, 3 patients got an excellent result, 8 good, 1 fair. CONCLUSION: PELD is effective in treating patient with upper lumbar disc herniation failing to respond to conservative treatment.
