Experimental Study Of Aerosol Foam Treatment Jingtongxiao Wide Anal Edema Model And Clinical Observation Of Inflammatory Hemorrhoids

GuangTongXiao Foam Aerosol(GTX) is invented by professor Zhao Baoming. Previous studies have shown the dosage form in the treatment of mixed hemorrhoids, anal fissure and other anorectal diseases has both features of traditional Chinese medicine and external treatment advantage. The dosage form has been widely used in foreign countries. GTX’s mechanism of relieving pain and spasmolysis has been confirmed. Anal edema caused by mixed hemorrhoid in clinical and pain in patients with symptoms,is an pressures for doctors to solve.The purpose of this study is repeating anal edema model in rats by croton oil, researching and discussing its anti-inflammation, detumescence and analgesic effects and mechanism on the anus edema model. And from the two aspects of conservative treatment and surgical treatment of clinical observation, to analyze that GTX can improve the situation of anal edema caused by inflammatory mixed hemorrhoid symptoms, to discuss inhibition of inflammatory cytokines and the mechanism of action of inflammatory mediators.2MethodsThis study is divided into three parts.The first part is the literature research. First concluding TCM etiology and pathogenesis of anal edema caused by mixed hemorrhoid, Western medicine theories of hemorrhoids, microscopic understanding of edema and vascular endothelial function, summarizing the current research progress of non-surgical therapy of traditional Chinese and western medicine treatment of inflammatory mixed hemorrhoid, these will help us find the point of animal experiment and clinical observation research on GTX foaming agent and the related factors of the meaning. Then including a meta analysis of external treatment of traditional Chinese medicine to inflammatory hemorrhoids. The last part of the literature research by summarizing the tutor professor Zhao Baoming’s clinical experiences, we can remember the review of GTX in the early period and my learning experiences. The second part is animal experiment parts. It mainly includes the experiment of building SD rats anal edema model by croton oil, the second is observing how GTX can treat the pain of the model, the third one is using enzyme-linked immune sorbent assay to measure TNF-a and IL-6,the last is using immunohisto-chemistry to measure iNOS. From these four aspects to prove GTX foam aerosol has the effect of analgesia, anti-inflammatory and detumescence to anal edema of rat model of inflammatory pain.The third part is the part of clinical observation. The first is an randomized controlled single-blind trial, to observe GTX foam aerosol using as a conservative treatment to outpatients who has the symptoms of anal edema by mixed hemorrhoids. and to record the symptoms integral before and after medication. The second clinical observation is using GTX foam aerosol to anal edema patients caused by mixed hemorrhoid before surgery, then measuring the content of iNOS,IL-6and TNF-a in postoperative hemorrhoid tissues and comparing them.3Results3.1the results of animal experiments3.1.1anal swelling model of SD rats caused by croton oilAfter the morphological changes and pathological section from SD rats which is anal swelling caused by croton oil, it can infer that the change of the model is in accordance with acute inflammatory change and also similar to acute onset hemorrhoids inflammatory change. The biopsy of GTX group is significantly changed, especially for mucosal epithelium and gland of the proximal anus. The lack of epithelium and glands just after molding can gradually complete after using GTX. The edema of submucosa, congestion of blood vessel. the expansion degree is also significantly reduce which is compared with model group.3.1.2analgesic effect of GTX foam aerosol to anal edema of rat modelMechanical withdrawal threshold and thermal withdrawal latency are comparable for each group before six hours.Mechanical withdrawal threshold comparison of each group six hours after building the model,P<0.05, the difference is statistically significant. It suggests there are differences between groups. Positive control group, the large and the middle dose of GTX group are changed after using medication, P<0.05, their significant difference is statistically significant. Six hours after giving medicine. MWT of each group are normal distribution, and variance. Model group, negative control group, GTX foam aerosol high-dose group and small dose group’s MWT value compared with the blank group, P<0.05, the difference is statistically significant. Positive control group and GTX middle-dose groups compared, P>0.05, there was no statistically significant difference.Thermal withdrawal latency comparison of each group six hours before building the model,P>0.05, no statistical significance, it prompts that each thermal pain threshold comparable. Thermal withdrawal latency of positive control group, GTX foam aerosol large dose group and middle dose group are changed significantly after using medicine,P<0.05, significant difference is statistically significant.Six hours after the treatment,the blank group and the GTX foam aerosol high-dose group compared with positive control group,P>0.05, there was no statistically significant difference.3.1.3the content of TNF-a and IL-6by using Elisa methodWith Elisa method, TNF-a and IL-6content of the normal group and model group serum have obvious differences, P<0.05. It is statistically significant. Anal edema of SD rats model by croton oil conforms to the inflammatory change.GTX has no obvious difference with indomethacin suppository group, P>0.05.It shows that indomethacin suppository effect is more obvious than GTX. The three groups of GTX compare with each other have no significant differences, P>0.05, temporarily it can’t explain each dose limit effect relationship. 3.1.4the content of iNOS by using immunohisto chemical methodUsing immunohistochemical method to observe the rats’crissum tissues, the expression of iNOS of each does GTX foam aerosol group are less than model group, more than control group. Especially the small dosage group increases obviously. Each dose GTX group comparing with model group and the blank group, there is no statistical difference by the study optical density value of immunohistochemical. GTX foam aerosol cannot infer it has no inhibition of iNOS.3.2the results of clinical observations3.2.1the clinic symptoms integral changesTo observe the clinic symptoms integral changes:the sex, age, course, mixed hemorrhoid stages of three groups are comparable, so are the pain, bloody, bearing-down pain, the prolapsed, the erosion of hemorrhoids mucosa and swelling of the situation before using treatments. GTX and indomethacin groups’scores of VAS decreased obviously after seven days’ therapy. The bloody symptom is the most obvious before using GTX foam aerosol, then it becomes the lowest one of the three groups. After using GTX for seven days,bearing-down pain decreased obviously than others. And GTX group for repairing hemorrhoids mucosal is superior to other two groups, the PUJI hemorrhoids suppository is better than indomethacin one.GTX is slower than indomethacin bolt on the size of the haemorrhoids detumescence effect, and is consistent with the changes of haemorrhoids swelling area.There is no statistically significant difference between these two groups.The overall efficient of GTX group (98.5%) is obviously higher than indomethacin suppository group (96.8%), and PUJI group (90.1%).3.2.2the expression of IL-6, TNF-a and iNOSby using immunohistochemical methodUsing immunohistochemical method to observe the expression of IL-6, TNF-a and iNOS from edema hemorrhoid tissues. The blank group are more positive expressed in three sets of pictures, GTX foam aerosol express less, the least is indomethacin suppository group.The immunohistochemical study optical density value comparison:GTX foam aerosol group compare with indomethacin suppository group for IL-6, P>0.05, for TNF-a and iNOS, P<0.05.Comparing with the blank group forIL-6and iNOS, P>0.05,for TNF-a,P<0.05.4ConclusionGuangTongXiao foam aerosol has the exact anti-inflammation, detumescence and analgesic effect in treating anal swelling SD rats model caused by croton oil.It also can stop the pain and reduce the swelling, repair the haemorrhoids mucosa, lift the location of haemorrhoids position of anal edema caused by mixed hemorrhoid,such as anal edema, pain, bloody and other symptoms. And the effect is better than indomethacin suppository group and PuJi group. We can conclude that Chinese traditional medicine in improving the bloody symptom and repairing the haemorrhoids mucosa is obviously better than indomethacin suppository. The mechanism of anti-inflammatory swelling and stoping the pain may be related to reducing the expression of TNF-a and IL-6for GuangTongXiao foam aerosol,Inhibiting the activation of iNOS,reducing the release of NO,so as to achieving the purpose of anti-inflammation, detumescence and analgesia. And the concentration-response relationships of each does of GTX deserve to be further discussed.