中西医结合治疗重型颅脑损伤及出血性中风并发应激性溃疡出血的效果观察

目的 探索重型颅脑损伤及出血性中风并发应激性溃疡出血的中西医结合治疗效果 ,以发挥中西医结合治疗的优势。方法 96例应激性溃疡出血患者被随机分为观察组 ( 4 8例 )和对照组 ( 4 8例 )。观察组在对照组常规治疗的基础上加用云南白药和白芨。结果 观察组显效率 72 92 % ,总有效率为 93 75 % ;对照组显效率 45 83 % ,总有效率为 77 0 9% ,经 χ2 检验 ,两组显效率差异有非常显著性 ( χ2 =7 43 ,P <0 .0 1) ,总有效率差异有显著性 ( χ2 =4 3 4,P <0 .0 5 )。

Doxycycline blocks gastric ulcer by regulating matrix metalloproteinase-2 activity and oxidative stress

AIM: To examine the effect of doxycycline on the activity of matrix metalloproteinases (MMPs) and oxidative stress in gastric tissues of rats following gastric injury.METHODS: Gastric ulcers were generated in rats by administration of 70% ethanol,and activity of doxycycline was tested by administration 30 min prior to ethanol.Similarly,the effect of doxycycline was tested in an indomethacin-induced gastric ulcer model.The activities and expression of MMPs were examined by zymography and Western blot analysis.RESULTS: Gastric injury in rats as judged by elevated ulcer indices following exposure to ulcerogen,either indomethacin or ethanol,was reversed significantly by doxycycline.Indomethacin-induced ulcerated gastric tissues exhibited about 12-fold higher proMMP-9 activity and about 5-fold higher proMMP-3 activity as compared to control tissues.Similarly,ethanol induced about 22-fold and about 6-fold higher proMMP-9 and proMMP-3 activities,respectively,in rat gastric tissues.Both proMMP-9 and MMP-3 activities were markedly decreased by doxycycline in ulcerogen treated rat gastric tissues.In contrast,the reduced MMP-2 activity in ulcerated tissues was increased by doxycycline during ulcer prevention.On the other hand,doxycycline inhibited significantly proMMP-9,-2 and -3 activities in vitro.In addition,doxycycline reduced oxidative load in gastric tissues and scavenged H2O2 in vitro.Our results suggest a novel regulatory role of doxycycline on MMP-2 activity in addition to inhibitory action on MMP-9 and MMP-3 during prevention of gastric ulcers.CONCLUSION: This is the first demonstration of dual action of doxycycline,that is,regulation of MMP activity and reduction of oxidative stress in arresting gastric injury.

Octreotide ameliorates gastric lesions in chronically mild stressed rats

AIM:To evaluate the effect of chronic mild stress(CMS) on the emergence of gastric ulcers and possible modulation by octreotide,a synthetic somatostatin analogue. METHODS:Adult male Wistar rats were subjected to nine different unpredictable random stress procedures for 21 d,a multifactorial interactional animal model for CMS.Octreotide was administered daily for 21 d at two dose levels(50 and 90μg/kg)before exposure to stress procedure.Macro-and microscopical assessments were made,in addition to quantification of plasma corticosterone and gastric mucosal inflammatory,oxidative stress, and apoptotic biomarkers. RESULTS:Exposure to CMS elevated plasma corticosterone(28.3±0.6μg/dL,P=0.002),an event that was accompanied by gastric lesions(6.4±0.16 mm,P=0.01) and confirmed histopathologically.Moreover,the insult elevated gastric mucosal lipid peroxides(13±0.5 nmol/g tissue,P=0.001),tumor necrosis factor-α(3008.6±78.18 pg/g tissue,P<0.001),prostaglandin E2(117.1 ±4.31 pg/g tissue,P=0.002),and caspase-3 activity (2.4±0.14 OD/mg protein,P=0.002).Conversely,CMS mitigated interleukin-10(627.9±12.82 pg/g tissue,P= 0.001).Furthermore,in animals exposed to CMS,octreotide restored plasma corticosterone(61%and 71%from CMS,P=0.002)at both dose levels.These beneficial effects were associated with a remarkable suppression of gastric lesions(38%and 9%from CMS,P=0.01)and reversal of derangements in gastric mucosa. CONCLUSION:The current investigation provides evidence that exposure to CMS induces gastric ulceration, which was alleviated by administration of octreotide possibly possessing antioxidant,anti-inflammatory,and anti-apoptotic actions.

Effect of moxa-burning heat stimulating Liangmen(ST 21) and Zusanli(ST 36) on proliferation and apoptosis signaling proteins in rats with stress-induced gastric ulcer

OBJECTIVE: To observe the effect of moxa-burning heat stimulating acupoints of Liangmen(ST 21)and Zusanli(ST 36) on the proliferation and apoptosis signaling proteins in rats with stress-induced gastric ulcer.METHODS: Forty rats were randomly divided into four groups: negative control(NC), ulcer control(UC), acupoints of stomach meridian(ASM), and acupoints control(AC). The acute gastric ulcer model was established by bound and water immersion.Rats in NC and UC groups didn't receive any moxa-burning heat stimulating treatment, while rats in ASM and AC groups were treated with buringmoxa heat stimulating the acupoints of Liangmen(ST 21) and Zusanli(ST 36) and their controlled points, respectively. Rats in all groups were sacrificed after 12 consecutive days treatment. The ulcer index was evaluated by using Guth's method.The expression of tumor necrosis factor-alpha(TNF-α), apoptotic protease activating facter-1(Apaf-1), Caspase-3, p21 activated kinase 1(PAK1),extracellular regulated protein kinases 2(ERK2),phosphorylated ERK2(p ERK2), phosphoinositide3-kinase(PI3K) and RAC-alpha serine/threonine-protein kinase(Akt) in gastric mucosa was detected by enzyme linked immunosorbent assay(ELISA).RESULTS: Compared with UC group, the ulcer index of ASM and AC groups decreased, and the injured gastric mucosa was improved, the expression of TNF-α, Apaf-1 and Caspase-3 in gastric mucosa was significantly reduced(P < 0.05), while the ex-pression of PAK1, ERK2, p ERK2, PI3 K and Akt in gastric mucosa was significantly increased(P < 0.05).And ASM showed better effect than AC group(P <0.05).CONCLUSION: Moxa-burning Heat stimulating of Liangmen(ST 21) and Zusanli(ST 36) could promote the recovery of gastric mucosal lesion probably by inhibiting cell apoptosis and promoting cell proliferation in stress-induced gastric ulcer.

The therapeutic effect of high-dose esomeprazole on stress ulcer bleeding in trauma patients

Purpose： To compare the therapeutic effects of different doses of intravenous esomeprazole on treating trauma patients with stress ulcer bleeding. Methods： A total of 102 trauma patients with stress ulcer bleeding were randomly divided into 2 groups： 52 patients were assigned to the high-dose group who received 80 mg intravenous esomeprazole, and then 8 mg/h continuous infusion for 3 days; 50 patients were assigned to the conventional dose group who received 40 mg intravenous esomeprazole sodium once every 12 h for 72 h. Results： Compared with the conventional dose group, the total efficiency of the high-dose group and conventional dose group was 98.08% and 86.00%, respectively （p 〈 0.05）, the hemostatic time was 22.10 h ± 5.18 h and 28.27 h ± 5.96 h, respectively （p 〈 0.05）. Conclusion： Both doses of intravenous esomeprazole have good hemostatic effects on stress ulcer bleeding in trauma patients. The high-dose esomeprazole is better for hemostasis.

Effects of the serum derived from rats treated with electroacupuncture at different meridian acupoints on EGFR signal transduction pathway in gastric mucosal cells

Objective To study the effect of the serum derived from the rats treated with electroacupunctre at Stomach Meridian acupoints on the EGFR signal transduction pathway in gastric mucosal cells. Methods Sixty rats were randomly divided into 5 groups： model group, Stomach （ST） Meridian group, Gallbladder （GB） Meridian group, ST＋ PD153035 group and GB＋ PD153035 group. Water-immersion and restrained stress method was adopted for preparation of the stress-induced gastric ulcer rat model, and the gastric mucosa cells were separated by using pronase digestion method. Gastric mucosa cells were incubated respectively with PD153035, EGFR inhibitor and the serum; PLCγ-1＇s expression level in gastric mucosa cells was tested by enzyme-linked immunosorbant assay （ELISA）, and PKC activity by isotope mingling method; and reverse transcription polymerase chain reaction assay （RT-PCR） was used for testing expression level of c-myc gene. Results The expression levels of PLCγ-1 ,PKC and c- myc gene were lower in gastric mucosa cells in the model group; there were relatively high expression levels of PLCγ-1 ,PKC and c-myc gene in the ST Meridian group and the GB Meridian group, with the highest expression levels of PLCγ-1 ,PKC and c-myc gene in the ST Meridian, and with a significant difference between the ST Meridian group and the GB Meridian group （P〈0.01 ） ; and relative lower expression levels of PLCγ-1, PKC and c-myc gene were seen in the ST ＋ PD153035 group and the GB ＋ PD153035 group; and there was a significant difference between the ST Meridian group and the ST ＋ PD153035 group （P〈0.01）. Conclusion There was a close correlation between the healing effect of electroacupuncture and activation of the EGFR signal transduction pathway in the impaired gastric mucosa cells, which was also one proof for the TCM theory： ＂There is relative specificity between the meridians and viscera＂.

Effect and Mechanism of Moxibustion on Acupoints Zusanli （ST 36） and Liangmen （ST 21） in the Prevention and Treatment of Stress Ulcer

Objective： To observe the effect of moxibustion on acupoints Zusanli （ST 36） and Liangmen （ST 31） on cell proliferation and cell apoptosis of gastric mucosa in rats with stress ulcer, investigatethe mechanism of moxibustion in promoting the repair of gastric mucosal injury at cellular and molecular levels, Methods： Sixty healthy Sprague-Dawley rats were randomly divided into four groups： the restraint control group, model group, moxibustion on acupoints group and moxibustion on non-acupoints group. Water immersion and restraint stress （WRS） was used to copy the stress ulcer model of rats, radio-immunoassay was used to detect the content of transforming growth factor （TGF-α）, and S-P immunohistochemical assay was adopted to determine the HSP70 expression, the proliferating cell nuclear antigen （PCNA） and cell apoptosis index in gastric mucosa. Results： For the WRS-induced gastric ulcer model of rat, the gastric mucosal injury （gastric ulcer index, UI） was increased, the content of TGF-α was decreased, PCNA was also decreased, HSP70 expression and cell apoptosis index were all increased （P〈0.01）, Moxibustion on acupoints Zusanli （ST 36） and Liangmen （ST 31） could decrease UI, increase the content of TGF-α, promote the expression of PCNA and HSP70, decrease cell apoptosis index in gastric mucosa, with significant differences when compared with the model group and control group （P〈0.01）. Conclusions： Moxibustion on acupoints Zusanli （ST 36） and Liangmen （ST 31） had protective effect on the gastric mucosa of stress ulcer, its mechanism may be promoting the TGF-α synthesis, stimulating cell proliferation in gastric mucosa and inhibiting cell apoptosis in gastric mucosa, and this process is related to the moxibustion-induced HSP70 expression.