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OBJECTIVE@#To explore the possible effects and mechanism of Zhizhu Decoction (ZZD) on the pathophysiology of slow transit constipation (STC).@*METHODS@#A total of 54 C57BL/6 mice was randomly divided into the following 6 groups by a random number table, including control, STC model (model), positive control, and low-, medium- and high-doses ZZD treatment groups (5, 10, 20 g/kg, namely L, M-, and H-ZZD, respectively), 9 mice in each group. Following 2-week treatment, intestinal transport rate (ITR) and fecal water content were determined, and blood and colon tissue samples were collected. Hematoxylin-eosin and periodic acid-Schiff staining were performed to evaluate the morphology of colon tissues and calculate the number of goblet cells. To determine intestinal permeability, serum levels of lipopolysaccharide (LPS), low-density lipoprotein (LDL) and mannose were measured using enzyme-linked immunosorbent assay (ELISA). Western blot analysis was carried out to detect the expression levels of intestinal tight junction proteins zona-occludens-1 (ZO-1), claudin-1, occludin and recombinant mucin 2 (MUC2). The mRNA expression levels of inflammatory cytokines including tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, IL-4, IL-10 and IL-22 were determined using reverse transcription-quantitative reverse transcription reaction. Colon indexes of oxidative stress were measured by ELISA, and protein expression levels of colon silent information regulator 1/forkhead box O transcription factor 1 (SIRT1/FoxO1) antioxidant signaling pathway were detected by Western blot.@*RESULTS@#Compared with the model group, ITR and fecal moisture were significantly enhanced in STC mice in the M-ZZD and H-ZZD groups (P<0.01). Additionally, ZZD treatment notably increased the thickness of mucosal and muscular tissue, elevated the number of goblet cells in the colon of STC mice, reduced the secretion levels of LPS, LDL and mannose, and upregulated ZO-1, claudin-1, occludin and MUC2 expressions in the colon in a dose-dependent manner, compared with the model group (P<0.05 or P<0.01). In addition, ZZD significantly attenuated intestinal inflammation and oxidative stress and activated the SIRT1/FoxO1 signaling pathway (P<0.05 or P<0.01).@*CONCLUSION@#ZZD exhibited beneficial effects on the intestinal system of STC mice and alleviated intestinal inflammation and oxidative stress via activating SIRT1/FoxO1 antioxidant signaling pathway in the colon.
Subject(s)
Mice , Animals , Sirtuin 1/genetics , Antioxidants , Occludin , Lipopolysaccharides , Claudin-1 , Mannose , Mice, Inbred C57BL , Constipation/drug therapy , Inflammation , Signal TransductionABSTRACT
Objective:To explore the clinical efficacy of modified Zhizhutang in treating senile primary constipation due to Qi-Yin deficiency and its influences on gastrointestinal neurotransmitters and gastrointestinal motility. Method:One hundred and twenty-one eligible patients were randomly divided into a control group （<italic>n</italic>=60） and an observation group （<italic>n</italic>=61）. On the basis of lifestyle adjustments， patients in the control group further received oral Qihuang Tongmi soft capsule，three capsules per time，three times per day， whereas those in the observation group were further treated with modified Zhizhutang，one bag per day， for eight successive weeks. The number of complete spontaneous bowel movements （CSBM， normal defecation was considered if CSBM ≥ three times per week） before and after treatment was recorded. The main symptoms of constipation，the patient assessment of constipation quality of life （PAC-QOL）， and the traditional Chinese medicine （TCM） syndrome before and after treatment were scored， followed by the anorectal pressure measurement and colonic transit test before and after treatment. The levels of somatostatin （SS），motilin （MTL），substance P （SP） and vasoactive intestinal peptide （VIP） before and after treatment were detected. Result:The weekly average number of CSBM in the observation group was greater than that of the control group （<italic>P</italic><0.01）， but the TCM syndrome score was lower than that of the control group （<italic>P</italic><0.01）. The normal defecation rate in the observation group was 57.38% （35/61），which was higher than 35% （21/60） of the control group （<italic>χ</italic><sup>2</sup>=6.092，<italic>P</italic><0.05）. The scores of the main symptoms of constipation in the observation group were significantly lower than those in the control group （<italic>P</italic><0.01）. The PAC-QOL subscale scores and the total score of the observation group significantly declined as compared with those of the control group （<italic>P</italic><0.01）. The anal resting pressure and anal maximum systolic pressure of the observation group were higher than those of the control group （<italic>P</italic><0.01），while the first sensation volume， urge sensation volume and maximum tolerable volume were lower （<italic>P</italic><0.01）. The excretion rates of markers in the observation group at 24 h，48 h and 72 h were significantly elevated in comparison with those in the control group （<italic>P</italic><0.01）. Compared with the control group， the observation group also exhibited increased serum MTL and SP （<italic>P</italic><0.01） and decreased SS and VIP （<italic>P</italic><0.01）. The recurrence rate in the observation group was 34.29% （12/35），obviously lower than 61.90% （13/21） in the control group （<italic>χ</italic><sup>2</sup>=5.051，<italic>P</italic><0.05）. The total effective rates in the observation group and the control group were 95.08% （58/61） and 81.67% （49/60） ， implying a significant difference （<italic>χ</italic><sup>2</sup>=5.321，<italic>P</italic><0.01）. Conclusion:For the elderly with primary constipation due to Qi-Yin deficiency， oral administration of modified Zhizhutang helps to regulate gastrointestinal neurotransmitters，improve gastrointestinal motility and gastrointestinal emptying rate， alleviate the symptoms of constipation， restore spontaneous bowel movements， improve their quality of life， and lower the recurrence rate. Its clinical effects were better than those of Qihuang Tongmi soft capsule.
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Objective::To observe the clinical efficacy of modified Zhishi Daozhiwan on slow transit constipation (STC) and the effect on gastrointestinal hormones and intestinal flora. Method::One hundred and sixty patients were randomly divided into control group and observation group by random number table. Patients in control group got Maren Wan, 1-2 pills/time, 2 times/days, and mosapride citrate tablets, 1 piece/time, 3 times/days. Patients in observation group got modified Zhishi Daozhiwan, 1 dose/day. A course of treatment was 4 weeks. Before and after treatment, the main symptoms of constipation and patient assessment of constipation symptoms (PAC-SYM) were scored. And times of spontaneous complete bowel movement (SCBM) and colonic transmission test were recorded. And levels of intestinal flora and motilin (MTL), vasoactive intestinal peptide (VIP), substance P (SP) and gastrin (GAS) were detected. The 12-week follow-up of patients (SCBM≥3) was recorded, and the relapse of disease was calculated. Result::According to rank sum test analysis, the clinical efficacy in observation group was better than that in control group (Z=2.275, P<0.05). After treatment, scores of the main symptoms of constipation, PAC-SYM, and the total score of PAC-SYM were all lower than those in control group (P<0.01). At the second, third and fourth weeks after treatment, the times of SCBM were more than those in control group (P<0.01). Ratio of residual marker at 24, 48 and 72 h was lower than that in control group (P<0.01). Count of enterococcus and enterobacter were lower than those in control group (P<0.01), while counts of bifidobacterium and lactobacillus were higher than in control group (P<0.01). Levels of GAS, MTL and SP were higher than those in control group, whereas level of VIP was lower than that in control group (P<0.01). And relapse rate in observation group was 33.85%, which was lower than 57.69% in control group (χ2=6.653, P<0.05). Conclusion::Modified Zhishi Daozhiwan can alleviate constipation and other symptoms, increase the number of SCBM, regulate gastrointestinal hormones and intestinal flora, and improve colonic transit function, with a good clinical efficacy and low recurrence rate, so it is worth clinical application.
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Objective:To observe clinical effect of addition and subtraction therapy of Xiaoyaosan combined with Simotang to irritable bowel syndrome with predominant constipation （IBS-C） and syndrome of stagnation of liver Qi and to study influence to gut-brain axis. Method:One hundred and forty-four patients were randomly divided into control group （72 cases） and observation group （72 cases） by random number table. The 66 patients in control group completed the therapy （2 patients were falling off or missing visit， 5 patients were eliminate）， 65 patients in observation group completed the therapy （4 patients were falling off or missing visit， 2 patients were eliminate）. Patients in control group got Simotang， 20 mL/time， 3 times/day. In control group， patients in observation group added addition and subtraction therapy of Xiaoyaosan combined with Simotang， 1 dose/day. And courses of treatment in two groups were 4 weeks. Before and after treatment， degree of abdominal pain， irritable bowel syndrome （IBS） symptom severity scale （IBS-SSS）， quality of life in irritable bowel syndrome （IBS-QOL）， syndrome of stagnation of liver Qi， scores of Hamilton anxiety scale-14（HAMA-14）， Hamilton depression scale-17（HAMD-17）， complete spontaneous bowel movement （CSBM）， response rate of abdominal pain and defecation， remission rate of IBS-SSS were all recorded. And levels of vasoactive intestinal peptide （VIP）， substance P （SP）， neuropeptide Y （NPY）， 5-hydroxytryptamine （5-HT）， somatostatin （SS） and calcitonin related gene peptide were detected， and safety was evaluated. Result:Degree of abdominal pain， scores of IBS-SSS， syndrome of stagnation of liver Qi ， HAMA-14， HAMD-17 and levels of VIP， NPY， 5-HT， SS and CGRP in observation group were all lower than those in control group （P<0.01）. And times of CSBM， score of IBS-QOL and level of SP were all higher than those in control group （P<0.01）. Besides， response rate of abdominal pain and defecation and remission rate of IBS-SSS in observation group 95.38%（62/65）， 93.85%（61/65） and 90.77%（59/65）were higher than 83.33%（55/66），78.79%（52/66）and 75.76%（50/66） in control group （P<0.05）. And curative effect of traditional Chinese medicine （TCM） syndromes in was better than that in control group （Z=2.1034， P<0.05）. No serious adverse events happened and no adverse reaction caused by TCM. Conclusion:Addition and subtraction therapy of Xiaoyaosan combined with Simotang can significantly ameliorate IBS-C symptoms， reduce bad mood， improve patients' quality of life， regulate a variety of brain gut peptide factors， and improve brain gut axis disorder. It has good clinical efficacy and safety.
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Objective::To observe effect of addition and subtraction therapy of Huaihuasan combined with Taohuatang to ulcerative colitis with cold-heat complicated syndrome at active stage, and to study regulation effect to immune function and inflammatory response. Method::One hundred and twelve patients were randomly divided into control group and observation group by random number table. Patients with light and middle symptoms in control group got mesalazine slow release tablets, 1.0 g/time, 3 times/days, patients with severe symptoms or whose symptoms were not changed after getting for 4 weeks in control group got prednisone acetate tablets, 0.75 mg·kg-1·d-1 for 3 times. Based on the treatment in control group, patients in observation group added Huaihuasan combined with Taohuatang, 1 dose/day. The course of treatment was 4 weeks. At remission period, mesalazine slow release tablets were used for maintain long-term maintenance therapy, 0.5 g/times, 3 times/days. Scores of disease activities were graded by improvement mayo, and clinical remission and clinical efficacy were recorded, scores of cold-heat complicated syndrome, mucous membrane under enteroscopy and histology of mucosa belongs to Geboes were graded. And levels of tumor necrosis factor-α(TNF-α) in peripheral blood, interleukin-8 (IL-8), IL-10, T lymphocyte subsets (CD4+, CD8+), and adverse reactions, 6 months' follow-up and recurrence were also be recorded. Result::Therapeutic effect of traditional Chinese medicine syndromes were analyzed by rank sum test, which in observation group was better than that in control group (Z=1.915, P<0.05). Clinical effect in observation group was 98.04%(50/51) higher than 84.00%(42/50) in control group, clinical remission rate was 94.12%(48/51) higher than 78.00%(39/50) in control group, and mucosal healing rate was 96.08%(49/51) higher than 82.00%(41/50) in control group (P<0.05). Scores of mayo, cold-heat complicated syndrome, colonic mucosa and index scores of Geboes were all lower than those in control group (P<0.01). And levels of TNF-α, IL-8 and CD8+ were lower than those in control group (P<0.01), and levels of IL-10, CD4+ and CD4+ /CD8+ were higher than those in control group (P<0.01). Recurrence rate during 6 months in observation group was 10.42%(5/48) lower than 30.77%(12/39) in control group (χ2=5.669, P<0.05), as for adverse reactions, there was no significant difference between two groups. Conclusion::Huaihuasan combined with Taohuatang can induce UC to remission period, inhibit the activity of disease, alleviate clinical symptoms, regulate immune function and expression of inflammatory factors, alleviate inflammatory reaction, promote intestinal mucosal healing, and can maintain clinical remission and reduce recurrence. The clinical efficacy is superior to that of 5-ASA/glucocorticoid in Western medicine.
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Objective:To observe the effects of addition and subtraction therapy of Danggui Shaoyaosan combined with Huaihuasan on ulcerative colitis (UC) with syndrome of dampness-heat in large intestine during active stage, and the effects on brain-gut petide neurotransmitter and inflammatory cytokines. Method:A total of 130 cases were included and randomly divided into control group and observation group, 65 cases in each group. In the control group, the patients received oral administration of mesalazine enteric-coated tablets, 1.0 g/time and 3 times/days. Severe patients received prednisone acetate tablets (0.75 mg·kg-1·d-1) in several times by oral administration. Based on the treatment in control group, patients in observation group also received addition and subtraction therapy of Danggui Shaoyaosan combined with Huaihuasan, 1 dose/day. Both groups were treated for 4 weeks. Symptom scores, Mayo scores, colonic mucosa scores and Inflammatory Bowel Disease Questionnaire (IBDQ) scores were assessed before and after treatment. Patients in remission stage were followed up for 6 months to record the recurrence. Before and after treatment, vasoactive intestinal peptide (VIP), substance P (SP), somatostatin (SS), interleukin-1 (IL-1), IL-6, IL-4 and IL-10 were detected. Result:After 4 weeks of treatment, the clinical remission rate was 93.22%in the observation group, better than 80.7%in the control group (χ2=4.035,PPPPχ2=4.509,PPPPPPConclusion:On the basis of conventional western medicine treatment, addition and subtraction therapy of Danggui Shaoyaosan combined with Huaihuasan in the treatment of UC (dampness-heat in large intestine) during active stage can control the disease activity in a short term, promote restoration of the colonic mucosa. And delay the recurrence in a long term, reduce the recurrence rate, regulate ghrelin neurotransmitters and pro-and anti-inflammatory cytokines levels.
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Objective:To observe clinical efficacy of Taohua Tang and Buzhong Yiqi Tang on Crohn's disease (CD) at active phase (deficiency-cold in spleen and stomach), in order to observed its effect on Th1 and Th17 cytokines. Method:According to random number table, 86 patients with CD were divided into control group (42 cases) and observation group (44 cases). The control group (mild) was given SASP, 3-4 g·d-1, Po, tid. The control group (moderate or poor efficacy of SASP) was given prednisone acetate, 0.75 mg·kg-1·d-1, Po, tid. Observation group was given Taohua Tang and Buzhong Yiqi Tang in addition to therapy of the control group, 1 dose·d-1. The course of treatment was 12 weeks. Before and after treatment, Best CDAI, SES-CD, IBDQ and deficiency syndrome were scored, and levels of CRP, ESR, ALB, HB, PLT, IFN-γ, TNF-α, IL-2 and IL-17 were measured before and after treatment. Result:After treatment, the effect of traditional Chinese medicine(TCM) syndromes in the observation group was better than that in the control group (Z=2.058, PPPPZ=2.112, PZ=2.288, PPPγ, TNF-α, IL-2 and IL-17 levels in the observation group were lower than those in the control group (PConclusion:In addition to the therapy of conventional western medicine, Taohua Tang and Buzhong Yiqi Tang in treatment of deficiency syndrome of Crohn's disease (CD) can control the activity degree of the disease, reduce the degree of illness and inflammation, and improve the remission rate and the quality of life, with a better clinical efficacy than the pure western medicine therapy.
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<p><b>OBJECTIVE</b>To investigate the clinical efficacy of rectocele repair with longitudinal incision and transverse suture on the vaginal posterior wall.</p><p><b>METHODS</b>One hundred and forty-six patients with rectocele were enrolled in our study from August 1999 to August 2003. The patients were randomly divided into two groups, and received traditional repair with longitudinal incision and longitudinal suture (control group, n=74) or repair with longitudinal incision and transverse suture on the vaginal posterior wall (study group, n=72). The efficacy and complications were compared between the two groups.</p><p><b>RESULTS</b>In the study group,only one case (1.4%) had no effect, and the total effective rate was 98.7%. The mean course of treatment was (11.0+/- 1.9) days. Only two cases (2.7%) had postoperative complication. In the control group, 8 cases (11.1%) had no effect, and the total effective rate was 88.9%. The mean course of treatment was (17.4+/- 1.6) days. Twenty-nine cases (40.3%) had postoperative complications. There were significant differences in the efficacy and complications between the two groups (both P< 0.01).</p><p><b>CONCLUSION</b>The refined rectocele repair with longitudinal incision and transverse suture on the vaginal posterior wall has good efficacy with shorter curative period and less complications.</p>