| Purpose:Prove the effectiveness of using Yu Dan Tang to prevent and cure clinical PCS(post-cholecystectomy syndrome) through clinical trials. Discuss the theoretical foundation of using Yu Dan Tang to prevent and cure PCS through analyzing the effects on the biliary pressure, the bile flow, and the bile composition and the accommodation to the motilin and the promote cholecystokinin of the rabbit whose gallbladder was removed given by Yu Dan Tang.Provide both theoretical and clinical foundation for popularize the application of using Yu Dan Tang to prevent and cure PCS in order to reduce the pain of patients treated with cholecystectomy.Material and method:First clinical trial1.Objects of study: 60 patients being treated by cholecystectomy due to benign gallbladder disease, who were elected based on inclusion criteria into the Department of General Surgery in Liaoning University of TCM Affiliated Hospital in the period of January, 2014 to September, 2015.2.Test method:All the patients were allocated randomly into control group(30 cases) and observation group(30 cases). The control group were treated conventionally in which anti-infective medicines,fluid infusion, vitamin supplements, maintaining aqueous electrolyte balance, and symptomatic support were used. Patients in control group start eating after exhausting. The observation group were treated Yu Dan Tang orally, 50 ml each time, 3 times per day, 4 weeks of continuous use on the second day, besides the treatments mentioned given to the control group.3.Observed indicators:(1)The happening of vomiting on the second day to the thirtieth day after the operation.(2)The cases of PCS in the two groups in half year to one and half years after the operation.(3)The detecting result of the liver function, the renal function, the motilin(MTL),cholecystokinin(CCK) and on the second day, the third day and the 30 th day after the operation.The second clinical trial1.Objects of study: 60 outpatients and hospitalized patients having PCS after being treated by cholecystectomy due to benign gallbladder disease, who were elected based on inclusion criteria into the Department of General Surgery in Liaoning University of TCM Affiliated Hospital in the period of January, 2014 to September, 2015.2.Test method: All the patients were allocated randomly into control group(30 cases) and observation group(30 cases). Every patient in groups filled the symptoms quantization tables truthfully. The control group were treated with amoxicillin, domperidone, Anethol trithione tablets, anisodamine tablet, and Smecta. They were reviewed in 3-6 weeks after symptomatic treatment, or reviewed at any time after the symptom disappeared, filling the symptoms ratings quantization tables. The traditional Chines medicine group were treated with Yu Dan Tang, 50 ml each time, 3 times per day, then were reviewed after being oral administered for 4weeks or reviewed at any time after the symptom disappeared filling the symptoms ratings quantization tables. Before dosing and after the treatment, the peripheral venous blood of patients being in fasting in the control group and the observation group were collected for future reference.3.Observed indicted(1)The total efficiency;(2)Significant efficiency;(3)Recurrence rate;(4)The changes of CCK and MTL in plasma before and after the treatment;(5)The blood routine, the stool routine, the urine routine, the liver function, the renal function, the ECG, the body temperature, the pulse, the respiration, the blood pressure of patients before and after the treatment.Animal trial1.Experimental materials(1)Experimental animals: 45 rabbits(2)Experimental medicines:(1)Sterile distilled water;(2)Yu Dan Tang;(3)Ketamine Hydrochloride Injection(3)Main reagents:(1)Rabbit motilin enzyme-linked immunosorbent assay kit(2)Rabbit cholecystokinin ELISA assay kit(3)Rabbit bile cholesterol test kit(4)Rabbit bile bilirubin test kit(5)Rabbit bile acid test kit(4)The main instruments(1)Homemade manometry catheter(2)Electrophysiological recorder(3)Pressure sensor(4)Automatic biochemical analyzer2Test methodFemale and male rabbits were allocated randomly into control group, model group, and experimental group. The rabbits in the control group were fed normally and received gavage using sterile distilled water without cholecystectomy. After the cholecystectomy modeling,the rabbits in the model group were infused sterile distilled water using stomach tube on the basis of normal feeding while the rabbits in the experimental group were infused Yu Dan Tang using stomach tube on the basis of normal feeding. After continuously being infused for3 weeks, the Common Bile Duct Pressure(CBDP), the Sphincter of Oddi Basal Pressure(SOBP), the Sphincter of Oddi Contractile Pressure(SOCP), the Sphincter of Oddi Contraction Frequency(SOCF), and the Sphincter of Oddi Contraction Time(SOCT) of rabbits in all the groups were measured when the bile flow of them were also measured and bile were collected for future reference. Rabbits’ blood was collected on ear vein for future reference as well.3.Observed indicators:(1)CBDP, SOBP, SOCP, SOCF, SOCT;(2)Bile flow per hour;(3)Bile composition: the content of TBA, IBIL and CHO;(4)The content of CCK and MTL in the venous blood.4.Statistical methodAll of the statistical works were processed with software package SPSS 17.0. the baseline characteristics of each groups were analyzed statistically in the first place. If the baseline characteristics have no differences, further statistical processing would be taken place.Experimental data is expressed with—X±s, Two samples which followed normal distribution in measurement data were examined with t-test; one-way ANOVA was applied among multiple samples. Samples which did not conform normal distribution were examined using Rank sum test; count data was examined with χ2-test. a<0.05 on each side meant that there was a significant difference. p<0.05 meant that there was statistical meaning. p<0.01 meant that there was significant statistical meaning.Result:The first clinical trial1.After the operation, the incidence of vomiting of the model group was 46.7%, and the incidence of vomiting of observation group was 20%. p<0.05, so the difference between two groups had significant statistical meaning that the incidence of vomiting of traditional Chinese medicine group was lower than the one of the control group.2.The incidence of PCS of the control group was 33.3%, while the one of the observation group was 10.34%. p<0.05, so the difference between two groups had statistical meaning that the incidence of PCS of the control group was higher than the one of the observation group.3.Comparing the CCK value(21.03±4.60) of the control group 2 days before the operation with the value(37.52±5.97) 3 days after the operation, q=45.2,p<0.01 which meant that there was significant statistical meaning that the CCK value 3 days after the operation was obviously higher than the one before the operation. Comparing the CCK value(28.63±4.67)of the control group 30 th day after the operation with the value 3 days after the operation,q=24.3,p<0.01 which meant that there was also statistical meaning that the CCK value 30 th day after the operation was obviously lower. Further comparing the CCK value of the control group 30 th day after the operation with the value 2 days before the operation, q=20.8,p<0.01 which meant that there was also significant statistical meaning that the CCK value 30 th day after the operation was obviously higher than the value before the operation. Comparing the CCK value(21.73±5.68) of the observation group 2 days before the operation with the value(36.30±7.86) 3 days after the operation, q=39.9,p<0.01 which meant that there was significant statistical meaning that the CCK value 3 days after the operation was obviously higher than the one before the operation. Comparing the CCK value(21.87±5.13) of the observation group 30 th day after the operation with the value 3 days after the operation,q=39.5,p<0.01 which meant that there was also significant statistical meaning that the CCK value 30 th day after the operation was obviously lower. Further comparing the CCK value of the observation group 30 th day after the operation with the value 2 days before the operation,q=0.38,p>0.05 which meant that there was no statistical meaning that the CCK value 30 th day after the operation was obviously higher than the value before the operation. The comparing result of the value of MTL was the same as the value of CCK.The second clinical trial1.Comparing the total points(13.33±2.28) of the control group before the operation with the total points(7.57±3.69) after the operation, t=9.83,p<0.01 which meant there was significant statistical meaning. The points being lower after the operation indicated that the PCS symptom of the patients in the control group was mitigated by the treatment with western medicine. Further comparing the points of every symptom, the result showed that western medicine was effective on the pain and discomfort of rib, nausea and anorexia, and diarrhea,but no effectiveness on bloating and intestine vector gas.Comparing the total points(13.83±2.25) of the observation group before the operation with the total points(2.93±2.64) after the operation, t=19.76,p<0.01 which meant there was significant statistical meaning. the points being obviously lower after the operation indicated that the traditional Chinese medicine, Yu Dan Tang, was effective on PCS. Further comparing the points of every symptom, the result showed Yu Dan Tang was effective on every symptom of PCS.Comparing the points of five symptoms and the total points after the operation, the results showed that the treatment effect of Yu Dan Tang was better than the one of western medicine.2.In the 30 cases in the control group, cured cases were 6.67%, effectual cases were 23.33%, effective cases were 43.33%, and ineffective cases were 26.67%. In the 30 cases in the observation group, cured cases were1 6.67%, effectual cases were 46.67%, effective cases were 30%, and ineffective cases were 6.67%. Comparing the total effective rate,χ2=4.32,p<0.05 which meant there was statistical meaning. The effective rate of the control group was 30% while the rate of the observation group was 63.33% which could indicate that the total effective rate of the observation group was higher than the rate of the control group,obviously. Therefore, the overall effect of the observation group was better than the effect of the control group.3.Before the treatment, the values of CCK of two groups had no difference. Comparing the value of CCK(25.66±6.28) of the control group before the operation with the value of CCK(21.21±4.62) after the operation, t=2.97,p<0.01 which meant there was significant statistical meaning and the CCK level went lower after being treated with western medicine. Comparing the value of CCK(25.28±6.30) of the observation group before the operation with the value of CCK(16.91±4.50) after the operation, t=6.35,p<0.01 which meant there was significant statistical meaning and CCK level went significantly lower after being treated with Yu Dan Tang as well. Comparing the CCK level changes after the treatment, t=3.65,p<0.01 which meant there was significant statistical meaning and CCK declined more obviously being treated with Yu Dan Tang than being treated with western medicine.4.Before the treatment, the values of MTL of two groups had no difference. Comparing the value of MTL(518.54±65.53) of the control group before the operation with the value of MTL(513.11±75.08) after the operation, t=0.24,p>0.05 which meant there was no statistical meaning and the MTL level did not change after being treated with western medicine.Comparing the value of MTL(509.35±68.99) of the observation group before the operation with the value of MTL(228.20±36.95) after the operation, t=20.00,p<0.01 which meant there was significant statistical meaning and MTL level went significantly lower after being treated with Yu Dan Tang as well. Comparing the MTL level changes after the treatment,t=18.65,p<0.01 which meant there was significant statistical meaning and the MTL level of the observation group was significantly lower than the level of the control group. This indicated that western medicine couldn’t change PCS patients’ MTL level, but Yu Dan Tang could lower it.5.8 cases in the control group relapsed while 2 cases in the observation group relapsed.χ2=5.01,p<0.05 which meant that there was statistical meaning that the probability of relapsing of the observation group was significantly lower than the one of the control group.6.Neither two groups of patients had adverse reactions which meant that using Yu Dan Tang to cure PCS was safe and reliable.Animal trial1.The changes of biliary system pressureComparing CBDP, control group(6.05±1.04), model group(10.46±1.31), experimental group(7.03±1.28), there were differences among the control group, the model group and the experimental group. p<0.01 which meant there was statistical meaning. the model group’s was higher than the other two groups’ s. No differences between experimental group’s and the control group’s indicated CBDP increased after cholecystectomy. After being treated with Yu Dan Tang, CBDP obviously decreased, and reach the CBDP level before the operation.Comparing SOBP of every groups, the model group’s(20.33±2.44) and the control group(11.73±2.22), q=16.65,p<0.01 which meant there was significant statistical meaning that model group’s was obviously higher than the control group’s. Comparing the experimental group’s(15.07±1.71) with the model group’s SOBP, q=10.19,p<0.01 which meant there was significant statistical meaning that the experimental group’s was lower than the model group’s.comparing it with the control group, q=6.47,p<0.01 which meant there was statistical meaning that the SOBP of the experimental group was higher than the control group’s. The result showed that SOBP increased after cholecystectomy; although it went lower after treatment with Yu Dan Tang, it did not reach the level before the operation.Comparing SOCP of every group, the model group(29.93±2.05) with the control group(18.8±2.08), q=21.55,p<0.01 which meant there was significant statistical meaning which the model group was higher than the control group. Comparing the experimental group(21.27±2.76) with the control group and the model group, p<0.01 which meant there was significant statistical meaning which the experimental group was obviously lower than the model group but higher than the control group. the result indicated that SOCP increased after the cholecystectomy and decreased after the treatment with Yu Dan Tang but did not reach the level before the operation.Comparing SOCF of every group, the model group’ s frequency was higher than the control group’s, p<0.05. The experimental group’s frequency was lower than the model group’s, p<0.05. There was no difference between the comparison with the control group’s.This indicated that SOCF went faster after the cholecystectomy and decreased after the treatment with Yu Dan Tang as the same as before the operation.Comparing SOCT of every group, the model group’ s was longer than the control group’ s,p<0.05. the experimental group’ s was shorter than the model group’ s, p<0.05. There was no difference between the comparison with the control group’ s. This indicated that SOCT got lengthen after the cholecystectomy and shorten after the treatment with Yu Dan Tang as the same as before the operation.2.The changes of bile flowComparing with the control group’ s bile flow(4.98±0.20), the bile flow of the experimental group(8.49±0.31) increased significantly. p<0.01 which meant there was significant statistical meaning. Comparing with the model group’s bile flow(5.01±0.28), the bile flow of the experimental group was significantly higher, p<0.01. There was no difference between the model group’ s bile flow and the control group’s bile flow.3.The changes of bile compositionComparing with the control group’ s content of TBA(6.11±1.81), the model group’s(7.05±1.65) was the same, p>0.05. The experimental group’s content of TBA(10.46±2.07) was higher than the other two, both p<0.01. The difference had significant statistical meaning.Comparing with the control group’ s content of CHO(3.43±0.50), the model group’ s(3.53±0.45) was the same, p>0.05. The experimental group’s content of CHO(1.48±0.45)was lower than the other two, both p<0.05. The difference had statistical meaning.Comparing with the control group’ s content of IBIL(6.99±0.67), the model group’s (7.12±0.41) was the same, p>0.05. The experimental group’s content of IBIL(5.24±0.66)was lower than the other two, both p<0.05. The difference had statistical meaning.4.The changes of gastrointestinal hormone levelsThe content of serum CCK in the model group(39.83±6.07) was obviously higher than the control group’s content(20.05±4.30), p<0.01, which meant the difference had significant statistical meaning. The experimental group’s content(28.24±4.30) was significantly lower than the model group’s content, p<0.01, which meant that the difference had significant statistical meaning. The experimental content was significantly higher than the control group’s content, p<0.01, which meant that the difference had significantly statistical meaning.This indicated that the level of serum CCK in rabbits significantly increased after the cholecystectomy, and decreased after the treatment with Yu Dan Tang but it was still higher than normal level.The content of serum MTL in the model group(75.97±17.92) was obviously higher than the control group’s content(34.79±8.93), p<0.01 which meant the difference had significant statistical meaning. The experimental group’s content(55.58±15.55) was significantly lower than the model group’s content, p<0.01 which meant that the difference had significant statistical meaning. The experimental group’s content was significantly higher than the control group’s content, p<0.01 which meant that the difference had significantly statistical meaning. This indicated that the level of serum MTL in rabbits significantly increased after the cholecystectomy, and decreased after the treatment with Yu Dan Tang but it was still higher than normal level.Conclusion:We found that patients had the secretion disorder of CCK and MTL indeed, which was the increasing of both through clinical trials. The changes of levels of CCK and MTL had close relations with the pathogenesis of PCS. Patients whose CCK and MTL decreased, had the lower disease incidence of PCS, which could show the causal relationship.By the animal trial, we found that rabbits’ CCK and MTL levels also increased after their gallbladders were resected, and the abnormal increasing of CCK made SO showed the status of high tension, showing the increasing of SOBP, SOCP, SOCF and SOCT. The bile was silted up, and the pressure of common bile duct increased. The increasing pressure could cause various clinical symptoms of PCS, and the abnormal increasing could also cause symptoms like bowel and diarrhea. Therefore, we can infer that CCK and MTL levels abnormally increasing was the cause of the PCS after cholecystectomy.From the animal trial we could see Yu Dan Tang released the high tense of SO, maintained smooth excretion of bile, and released the high-pressure state of the common bile duct so that the pressure of the bile duct could be back to normal. Basing on this foundation and combining the clinical test result, we could know the Yu Dan Tang could prevent and cure PCS by decreasing CCK and MTL levels. It was significantly effective on the pain and discomfort of rib, nausea and anorexia, diarrhea, and bloating and intestine vector gas, and more effective than the western medicine. Yu Dan Tang also could change bile composition,increase TBA, lower CHO and IBIL. Meanwhile, it was helpful to gallbladder and the emission of bile to the duodenum to diagnose as well as the cholestasis in the common bile duct which was beneficial to clearing the residual stones and preventing stones in bile duct.Overall, Yu Dan Tang has lasting effect on PCS and its relapsing rate is low. This medicine is safe and reliable. It is worthy to further popularize and apply this medicine clinically when it also provides new thinking of studying using traditional Chinese medicine to prevent and cure PCS. |
PDF Full Text Request