Wang Gao-Hua, Dong Hai-Yan, Dong Wei-Guo, Wang Xiao-Ping, Luo He-Sheng, Yu Jie-Ping
Department of Mental Health Center, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuhan 430060, Hubei Province, China.
World J Gastroenterol. 2005 Mar 7;11(9):1373-7. doi: 10.3748/wjg.v11.i9.1373.
To investigate the abnormity of rat colon caused by depression and the ameliorative effects of Radix Acanthopanacis Senticosi (RAS) capsule on colon and their mechanisms in rat depression model.
Chronic stress-induced model of depression of Wistar rats was produced. The experimental animals were randomly divided into model control, 5-aminosalicylic acid (5-ASA) therapy group and three RAS capsule therapy groups. These five groups were intracolonically treated daily (8:00 a.m.) for 2 wk with normal saline, 5-ASA (100 mg/kg) and RAS capsule at the doses of 300, 600 and 900 mg/kg, respectively. A normal control group of rats was also included in the study. Colonic activities of nitric oxide (NO) and superoxide dismutase (SOD), levels of malondialdehyde (MDA) and inducible nitric oxide synthase (iNOS) were determined by ultraviolet spectrophotometry. The expression of cyclooxygenase-2 (COX-2) in colonic tissue was detected by immunohistochemistry.
Enhanced colon inflammatory response and oxidative stress were observed in the chronic stress-induced rat depression model, which manifested as the significant increase of MDA, iNOS and NO levels, as well as the expressions of COX-2 in the colon tissue, but the colonic SOD activity was significantly decreased compared with the normal control (MDA: 10.34+/-2.77 vs 2.55+/-0.70; iNOS: 1.11+/-0.44 vs 0.25+/-0.16; COX-2: 53.26+/-8.16 vs 4.87+/-1.65; NO: 11.28+/-5.66 vs 4.76+/-1.55; SOD: 53.39+/-11.15 vs 84.45+/-22.31; P < 0.01). However, these parameters were significantly ameliorated in rats treated locally with RAS capsule at the doses of 300, 600 and 900 mg/kg (iNOS: 0.65+/-0.31, 0.58+/-0.22 and 0.64+/-0.33; NO: 5.99+/-2.73, 6.87+/-1.96 and 6.50+/-1.58; MDA: 2.92+/-0.75, 3.19+/-1.08 and 3.26+/-1.24; SOD: 70.81+/-12.36, 73.30+/-15.30 and 69.09+/-11.03, respectively). The expressions of COX-2 in the colon were significantly ameliorated (28.83+/-9.48 and 27.04+/-9.56, respectively) when RAS capsule was administered at the doses of 600 and 900 mg/kg.
Administration of RAS capsule intracolonically may have significant therapeutic effects on the colon of rat depression model, which are probably due to its antioxidative action and inhibition of arachidonic acid metabolism.
探讨抑郁所致大鼠结肠异常以及刺五加胶囊对大鼠抑郁模型结肠的改善作用及其机制。
制备Wistar大鼠慢性应激性抑郁模型。将实验动物随机分为模型对照组、5-氨基水杨酸(5-ASA)治疗组和三个刺五加胶囊治疗组。这五组分别每天上午8:00结肠内给予生理盐水、5-ASA(100mg/kg)以及剂量分别为300、600和900mg/kg的刺五加胶囊,持续2周。研究中还设正常对照组。采用紫外分光光度法测定结肠一氧化氮(NO)和超氧化物歧化酶(SOD)活性、丙二醛(MDA)和诱导型一氧化氮合酶(iNOS)水平。采用免疫组化法检测结肠组织中环氧化酶-2(COX-2)的表达。
在慢性应激诱导的大鼠抑郁模型中观察到结肠炎症反应和氧化应激增强,表现为MDA、iNOS和NO水平以及结肠组织中COX-2表达显著增加,但结肠SOD活性与正常对照组相比显著降低(MDA:10.34±2.77对2.55±0.70;iNOS:1.11±0.44对0.25±0.16;COX-2:53.26±8.16对4.87±1.65;NO:11.28±5.66对4.76±1.55;SOD:53.39±11.15对84.45±22.31;P<0.01)。然而,给予剂量为300、600和900mg/kg的刺五加胶囊局部治疗的大鼠,这些参数得到显著改善(iNOS:0.65±0.31、0.58±0.22和0.64±0.33;NO:5.99±2.73、6.87±1.96和6.50±1.58;MDA:2.92±0.75、3.19±1.08和3.26±1.24;SOD:70.81±12.36、73.30±15.30和69.09±11.03)。当给予600和900mg/kg剂量的刺五加胶囊时,结肠中COX-2的表达显著改善(分别为28.83±9.48和27.04±9.56)。
结肠内给予刺五加胶囊可能对大鼠抑郁模型的结肠具有显著治疗作用,这可能归因于其抗氧化作用和对花生四烯酸代谢的抑制。