The Effects And Mechanisms Of Capsaicin On The Rat Gastric Motility In Different Dose And Periods

Objective: TO rastresearch the effects and mechanisms of capsaicin on the rat gastric motility in different dose and periods. Methods : ? the grouping:the experiment is divided into experimental group and the control group D. The experimental group according to different dose is divided into group A,B,C.Group A, group B and group C were given CAP 0.1 mg/kg/d, 1 mg/kg/d, 5 mg/kg/d.(2)the installment:the experiment is divided into 4 period,installment method:?period for 3 days, ?period for 1 week, ?period for 2 weeks, IVperiod for 4 weeks.Each group according to the installment method divides into four small groups.For example, group A is divided into group A1,A2, A3, A4 respectively corresponding to 4 period, 10 rats per small group, totally 160 rats.(3)the preparations of CAP: take 1 mg, 10 mg, 50 mg CAP,respectively.After weighing,the CAP are fully dissolved in 10% twain 20 ml+ of 10% alcohol 1 ml + 0.9% saline 79 ml CAP solvents,respectively.(4)CAP dosing method: Group A: 0.01mg/ml CAP solution lavageing, 0.1 mg/kg/d,once a day.Then give ordinary feed, free water.Group B: 0.1mg/ml CAP solution lavageing, 1mg/kg/d,once a day.Then give ordinary feed, free water.Group C: 0.5mg/ml CAP solution lavageing, 5mg/kg/d,once a day.Then give ordinary feed, free water.Group D: 2.5 ml CAP solvent lavage, one time a day.Then give ordinary feed, free water.(5)Measurements:(1)general situation: to observe rat's state of mind, appetite, urine and other general situationn in the process of the experiment.(2)Nuclide imaging method is used to detect the gastric emptying, record all the rat gastric half emptying time(T50 %), the determination of 65 min gastric emptying rate(GE65 %).(3)The rat gastric mucosal barrier detection:after the completion of gastric emptying measurement,3% pentobarbital sodium executed rats, remove full the stomach, cut open along the greater curvature stomach, saline rinse,naked eye observing the mucous membrane,improved the Guth standard grading standard to evaluate the gastric mucosal damage; take 1 piece of gastric tissues for HE dyed histologic examination, adopting Masuda standard to evaluate the gastric mucosa pathological damage.(4) Immunohistochemical detection of gastric mucosathe expression of TRPV1, CGRP and SP, and color pathological image analysis software analysis indicators of positive index.Results: 1. The general situation of rats: all experimental rats good mental state, flexible operation, poor appetite, surface smooth, urine is normal, no death. 2. Rat gastric half emptying time T50%(min) : group A1, A2, A3, A4 T50 %(min), respectively is:32.36±5.86(min)?35.18±6.73(min)?36.91±4.77(min) ?29.32±3.26(min);group B1, B2, B3, B4 T50 %(min), respectively is:42.06±4.99(min)?44.93±7.88(min)?34.05±5.29(min)?23.87±3.59(min);group C1, C2, C3, C4 T50 %(min), respectively is:45.65±6.73(min)?41.35±5.92(min)?29.56±5.58(min)?25.79±4.52(min);group D1?D2?D3?D4T50%(min),respectively is:23.15±4.52(min)?26.17±4.33(min)?26.89±6.93(min)?22.56±4.98(min)?(1) Group A and group D rat T50 %(min) comparing :the rats gastric half emptying time of group A1, A2, A3, A4 were longer than group D1, D2, D3, D4(P < 0.05).(2)Group B and group D ratT50 %(min) comparing : the rats gastric half emptying time of group B1, B2, B3 were longer than group D1, D2, D3(P < 0.05).(3)Group C and group D rat T50 %(min) comparing :the rats gastric half emptying time of group C1, C2 were longer than group D1, D2(P < 0.05).(4)Group A and group B rat T50 %(min) comparing:the rat gastric half emptying time of group A1, A2 were significantly shorter than the rat gastric half emptying time of group B1, B2(P < 0.05), A4 group rats gastric half emptying time were longer than B4 rat gastric half emptying time(P < 0.05).(5)Group A and group C rat T50 %(min) comparing:the rat gastric half emptying time of group A1, A2 were significantly shorter than the rat gastric half emptying time of group C1,C2(P < 0.05), the rats gastric half emptying time of group A3 were longer than group C3(P<0.05).(6) group B compared with group C periods every period has no statistical significance.(7)Every period of group A compare to each other: Compared to A1 and A2, A3, A4, there is no obvious difference.No statistical significance compared A2 and A3.But the A4 rat gastric half emptying time is significantly reduced, when compared with the A2, A3,it was statistically significant(P < 0.05).(8) Every period of group B compare to each other:rat gastric half emptying time of B1 were shorter than B2(P > 0.05).Rat gastric half emptying time of B1 were longer than B3 and B4(P < 0.05).Rat gastric half emptying time of B2 were longer than B3 and B4(P < 0.05), B3 rat gastric half emptying time were also significantly prolonged than B4,obviously(P < 0.05).(9)Every period of group C compare to each other:Rat gastric half emptying time of C1 were longer than C3 and C4(P < 0.05).Rat gastric half emptying time of B2were longer than B3 and B4(P < 0.05).(10)Every period of group D compare to each other were no statistical significance.3.65 min of rats gastric emptying rate(GE65min%): group A1, A2, A3, A4 GE65min% respectively is: 59.36±8.86?61.18±6.73?62.01±5.77?63.32±7.26;group B1, B2, B3, B4 GE65min% respectively is: 58.31±13.78?61.10±7.88?61.93±6.29?68.74±13.59;group C1, C2, C3, C4 GE65min% respectively is: 60.39±10.74?62.44±7.56?65.17±12.44?70.53±7.56;group D1, D2, D3, D4 GE65min% respectively is: 76.17±13.56?74.93±10.78?71.35±14.30?73.82±11.46.A, B, C compare to D group :A1 < D1 group(F = 2.342, P = 2.342), A2 <D2 group(F = 2.566, P = 0.003), A3 < D3 group(F = 4.544, P = 4.544), A4 < D4 groups(F = 2.492, P = 2.492).B1 < D1 group(F = 0.968, P = 0.968), B2 <D2 group(F = 1.871, P = 1.871), B3< D3 group(F = 3.824, P = 3.824).C1 < D1 group(F = 1.594, P = 1.594), C2< D2 groups(F = 2.033, P = 2.033). C3 and C4 compared to D3 and D4 group had no statistical significance. 4.The rat gastric mucosa tissue TRPV1 optical density(PI) value: group A1, A2, A3, A4 PI value respectively is:1.83±0.22?1.89±0.18?1.87±0.14?1.93±0.14;group B1, B2, B3, B4 PI value respectively is:1.82±0.20?1.90±0.24?1.94±0.27?1.87±0.20;group C1, C2, C3, C4 PI value respectively is:1.89±0.26?1.95±0.29?1.93±0.22?1.85±0.25;group D1, D2, D3, D4 PI value respectively is:1.57±0.17?1.64±0.15?1.65±0.21?1.59±0.16?(1)A1 > D1 groups(F = 0.597, P = 0.008), A2 > D2 group(F = 0.465, P = 0.037), A3 > D3 group(F = 2.250, P = 2.250), A4 > D4 group(F = 1.316, P < 0.05).(2) B1 >D1 groups(F = 0.723, P = 0.007), B2 > D2 group(F = 0.391, P = 0.391), B3 > D3 group(F = 0.065, P = 0.015, B4 > D4group(F = 0.391, P = 0.391).(3)C1 > D1 groups(F = 0.428, P = 0.04), C2 > D2 group(F = 0.268, P = 0.268), C3 > D3 group(F = 0.911, P = 0.911), C4 > D4 groups(F = 0.64, P < 0.05),(4)group A and group C, group A and group B, group B and group C has no statistical significance.(5)The gastric mucosa tissue TRPV1 optical density(PI) of A, B, C, D group each periods were no statistical significance. 5.The rat gastric mucosa tissue CGRP optical density(PI) value:group A1, A2, A3, A4 PI value respectively is:3.93±0.42?3.61 ± 0.48 ? 3.29 ± 0.34 ? 3.31 ± 0.46; group B1, B2, B3, B4 PI value respectively is:4.72±0.50?4.68±0.52?3.63±0.57?3.10±0.39;group C1, C2, C3, C4 PI value respectively is:4.89±0.56?4.95±0.48?3.18±0.52?2.95±0.45;group D1, D2, D3, D4 PI value respectively is:2.57±0.47?2.64±0.55?2.75±0.61?2.69±0.56.(1)A1 > D1 group(F = 1.252, P < 0.05), A2 > D2 groups(F = 2.095, P < 0.05), A3> D3 group(F = 3.325, P = 3.325), A4 > D4 groups(F = 1.482, P = 1.482).(2) B1 > D1 group(F = 0.884, P < 0.05), B2 > D2 groups(F = 1.119, P < 0.05), B3> D3 group(F = 1.183, P = 1.183),B4 group compared with D4 group had no statistical significance.(3)C1 > D1 group(F = 0.704, P < 0.001), C2 > D2 groups(F = 1.313, P < 0.05).C3 and C4 group compared with D3, D4 group had no statistical significance.(4)gastric mucosa tissue CGRP optical density(PI) value of group A1, A2 were significantly less than group B1, B2(P < 0.05).(5)Gastric mucosa tissue CGRP optical density(PI) value of group A1, A2 were significantly less than group C1, C2(P < 0.05). C4 group rat gastric mucosa CGRP expression decreased significantly, and much smaller than A4 group has statistical significance.(6)Gastric mucosa tissueCGRP optical density(PI) value of group B1,B2,B4 comparing with C1, C2 and C4 group were no difference(P > 0.05), the C3 < B3 group(P < 0.05).(7)Each periods of group A in the rat gastric mucosa CGRP optical density(PI) value comparison: A1 > A3(P < 0.05), A2 > A4(P < 0.05), A1 > A4(P < 0.05).(8)Each periods of group B in the rat gastric mucosa CGRP optical density(PI) value comparison:B2>B3(P<0.05),B1 > B3(P < 0.05), B2 > B4(P < 0.05), B1 > B4(P < 0.05), B3 > B4(P < 0.05).(9)Each periods of group C in the rat gastric mucosa CGRP optical density(PI) value comparison: C2 > C3(P < 0.05), C1 > C3(P < 0.05) C2 > C4(P < 0.05), C1 > C4(P < 0.05).(10)Each periods of group D in the rat gastric mucosa CGRP optical density(PI) value comparison were no obvious change.6.The rat gastric mucosa SP optical density(PI) value: group A1, A2, A3, A4 PI value respectively is:1.28±0.18?1.27±0.14?1.27±0.11?1.30±0.17;group B1, B2, B3, B4 PI value respectively is:1.30±0.10?1.24±0.12?1.26±0.11?1.29±0.09;group C1, C2, C3, C4 PI value respectively is:1.29±0.22?1.25±0.14?1.28±0.13?1.30±0.19;group D1, D2, D3, D4 PI value respectively is:1.27±0.17?1.23±0.11?1.26±0.15?1.29±0.12.(1)rat gastric mucosa SP expression of A, B, C group compared with group D corresponding periods had no statistical significance.(2)rat gastric mucosa SP expression of A group compared with group B corresponding periods had no statistical significance.(3)rat gastric mucosa SP expression of A group compared with group C corresponding periods had no statistical significance.(4)rat gastric mucosa SP expression of B group compared with group C corresponding periods had no statistical significance.(5)The gastricmucosa tissue SP optical density(PI) of A, B, C, D group each periods were no statistical significance. 7.Gastric mucosal damage index: macroscopic observation all the experimental group and control group rats gastric mucosa were smooth, no obvious bleeding, erosion. According to the Guth improved score, are all zero.Gastric mucosal injury pathological score: HE staining were observed under optical microscope: all specimens mucosa structure complete, deep glands order, no inflammatory cell infiltration, organization is complete.The experimental group and control group in the rat gastric mucosa Masude score difference has no statistical significance(P > 0.05).Conclusion: 1. CAP inhibiting gastric dynamics:normal rats were given CAP solution 0.1mg/kg,1mg/kg, 5mg/kg though lavage,3 day-4 weeks, all show that the effect of inhibition of gastric emptying.And the greater the dose the stronger the inhibition.Over time, increased tolerance of rats for CAP, the inhibition effect weakened gradually.2.The rat gastric mucosa TRPV1 expression can be raised by CAP, but the increases TRPV1 expression effects of CAP had no difference bettween different dosage,different time CAP lavage. 3. CAPcan promote the release of CGRP, the more dose of CAP the greater the CGRP release.4.CAP lavage can not influence the release of SP. 5.Given CAP 0.1 mg/kg, 1 mg/kg, 5 mg/kg lavage had no obvious effect on mucosal barrier in rats.