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The Study on Mechanism of Botulinum Toxin-A on Gastric Motility in Rats

Author: LiuWenHui
Tutor: LiuQingSen
School: PLA Postgraduate Medical School
Course: Digestion within the science
Keywords: botulinum toxin A rat antrum gastric empty gastrointestinal hormone
CLC: R573
Type: Master's thesis
Year: 2005
Downloads: 53
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Abstract


[Background and aims] Botulinum Toxin-A exerts its paralytic action on gastrointestinal smooth muscle by binding strongly to presynaptic cholinergic nerve terminals at the neuromuscular junction to inhibit acetylcholine release .In nineteen ninety-three, Pasricha et al injected BTA in lower esophagus sphincter(LES) to treat the patients with achalasia successfully. After that, the use of BTA for various gastrointestinal diseases has been focused, including sphincter of oddi dysfunction、 outlet obstructive constipation、 anismus、 chronic anal fissure , and the results were remarkable. In two thousand years, foreign scholars reduced weight of animals and obesity patients by injection BTA in their antrum smooth muscle. However, they could not expound its role mechanism. In this experiment, BTA was injected in antrum smooth muscle of rats to investigate its effect , and some alimentary hormones were evaluated, which provided some new evidence for more extended indication of BTA. [Methods] Wistar rats of postnatal nine weeks were divided into four groups:small dose group, middle dose group, large dose group and control group. Each rat was laparotomized injected BTA solution 0.4ml or saline 0.4ml. During the subsequent twelve weeks, weight and diet of every rat in four groups were register. Then, gastric semi-empty time(min) was determined by nuclide scan to evaluate the effect of BTA on gastric dynamic. The contents of CCK、 VIP、 AChE、 MTL and LEP were measured by immunohistochemistry method and radio-immunity method in order to evaluate the effect of BTA on secrete and expression of these hormones. Data were packed up by Stata 7.0 statisticalsoftware, and P<0.05 was thought significantly. The staining results were analyzed semi-quantitatively by computerized color image analyzer using the following parameters: integrated opticaldensity (IOD), immunore active area percent and immunoreactive area.[Results] Diet and weight were significantly lower in middle and large dose group than those in control group, ( P<0.05). But in only short time diet and weight were significantly lower in small dose group than those in control group, ( P<0.05 ) . At the twelveth weekend, gastric semi-empty time in small dose group were 110.5 ± 26.67 min, which were longer than control group (86.83 ± 2.98 min ) , but it was no statistic difference,( .B>0.05). Middle dose group (161.67±23.53 min) and large dose group(200.33±44.37 min) were significantly longer than control group(86.83±22.98 min),(P<0.05) . Plasm motilin in small dose group was 114.49±15.93 pg/ml, compared with control group, it was no statistical meaningful (P>0.05). Middle dose group(80.56±10.43 pg/ml) and large dose group (65.99±10.50 pg/ml) were significantly lower than control group (123.65±31.1O pg/ml), ( P<0.05) . The level of serum leptin ( small dose group 0.99±0.13ng/ml, middle dose group 0.97±0.18ng/ml, large dose group 0.83±0.23 ng/ml) were significantly lower than control group(l.28±0.25 ng/ml), ( P<0.05 ) . The results of immunohistochemistry revealed that IOD of the CCK expressed in antrum mucosa and myenteric plexus in large dose group ( 140.79±56.77 and 139.83±37.39) were much higher than those in control group(68.65± 15.86 and 77.91±32.2l),(.F<0.05). IOD of AChE positive-staining in antrum mucosa and myenteric plexus in middle dose group( 66.44±9.74 and 72.44±18.43) and in large dose group (63.21±12.66 and 68.38±10.60) were much lower than those in control group( 91.58±10.43 and 98.05±16.53), (P<0.05 ) . IOD of VIP

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