阳和化岩汤对大鼠乳腺癌癌前病变的抑制及ki67表达的影响

Effect of Yanghe Huayan Decoction on Precancerosis of Breast Cancer,Protein and mRNA Expression of ki67:an Experimental Research

目的探讨阳和化岩汤对大鼠乳腺癌癌前病变的抑制作用以及对ki67蛋白及mRNA表达的影响。方法采用二甲基苯并蒽(DMBA)诱导建立大鼠乳腺癌癌前病变模型,9周后随机分为空白对照组、模型组、阳和化岩汤组、散结化痰汤组、平消片组及三苯氧胺组,每天分别采用饮用水、阳和化岩汤(组成:鹿角霜1 2 g熟地9 g肉桂6 g白芥子3 g莪术12 g山慈菇1 5 g浙贝母9 g甘草6 g)7.2 g/kg、散结化痰汤(组成:白花蛇舌草15 g半枝莲15 g栝蒌15 g半夏9 g)5.4 g/kg、平消片144 mg/kg及三苯氧胺4 mg/kg灌胃治疗4周。取大鼠乳腺组织,HE染色观察病理形态学变化,免疫组化法检测ki67蛋白表达的阳性率和灰度值,q-PCR检测ki67 mRNA表达。结果与模型组比较,其他各治疗组一般增生与癌前病变发生率高,浸润性癌发生率低,差异有统计学意义(P<0.05);除散结化痰汤组外,其他治疗组ki67蛋白表达灰度值升高,差异有统计学意义(P<0.05,P<0.01);ki67阳性率及ki67 mRNA表达除平消片组外均下降,差异均有统计学意义(P<0.05,P<0.01)。与阳和化岩汤组比较,各治疗组癌前病变与浸润性癌发生率差异无统计学意义(P>0.05);平消片组ki67表达阳性率及ki67 mRNA表达均升高,差异有统计学意义(P<0.05)。结论阳和化岩汤能够部分阻断逆转乳腺癌癌变,并具有抑制ki67蛋白及mRNA表达的作用,其作用优于平消片,与三苯氧胺接近,适用于乳腺癌癌前病变的预防治疗。

Objective To explore the effect of Yanghe Huayan Decoction （YHD, a representa- tive recipe for warming yang mass dissipating） in inhibiting precancerosis of breast cancer （PBC） and on the protein and mRNA expression of ki67. Methods The PBC rat model was established by dimethyl- benzanthracene （DMBA）, and 9 weeks later rats were randomly divided into the blank control group, the model group, the YHD group, the Sanjie Huatan Decoction group （SHD）, the Pingxiao Tablet group （PT）, and the tamoxifen group. Rats in the model group were administered with water by gastrogavage. Rats in the YHD group received YHD （deglued antler powder 12 g, prepared rhizome of rehmannia 9 g, cassia bark 6 g, white mustard seed 3 g, zedoary root 12 g, appendiculate cremastra pseudobulb 15 g, chekiang fritillary bulb 9 g, licorice root 6 g） at the daily dose of 7.2 g/kg by gastrogavage. Rats in the SHD group received SHD （oldenlandia diffusa 15 g, Scutellaria Barbata 15 g, Trichosanthes Kirilowii 15 g, pinellia 9 g） at the daily dose of 5.4 g/kg by gastrogavage. Rats in the PT group received PT at the dai-ly dose of 144 mg/kg by gastrogavage. Those in the tamoxifen group received tamoxifen at the daily dose of 4 mg/kg by gastrogavage. Pathomorphological changes of the breast tissue were observed by HE stai- ning. The positive rate and the gray value of ki67 expression were detected by immunohistochemical as- say. And the expression of ki67 mRNA was detected by q-PCR. Results Compared with the model group, the general hyperplasia and the occurrence rate of precancerous lesion were higher and the oc- currence rate of invasive carcinoma was lower in each treatment group （P 〈0.05）. Except the SHD group, the intensity of ki67 grey value increased in each treatment group （P 〈0.05, P 〈0.01 ）. Except the PT group, the positive rate of ki67 and mRNA expression of ki67 increased in the rest treatment groups （P 〈0.05, P 〈0.01 ）. Compared with the YHD group, there was no statistical difference in the oc- currence rate of infiltration or the occurrence rate of precancerous lesion （P 〉0.05）. The positive rate of ki67 expression and mRNA expression of ki67 increased in the PT group, showing statistical difference （P 〈 0.05）. Conclusions YHD could partially inhibit and reverse canceration of breast cancer. It also could inhibit ki67 protein and mRNA expression. Its effect was similar to tamoxifen and superior to PT. So it was suitable for prevention and treatment of precancerous lesion of breast cancer.