从“肾毒”论治慢性肾脏病＊

慢性肾脏病是一种以肾脏功能的损伤为主要表现，并可累及全身多脏器的慢性进展性疾病。中医辨证治疗本病在延缓病情、改善预后等方面具有显著的优势。通过中医理论研究及临床经验总结，笔者提出从“肾毒”论治慢性肾脏病，认为其不仅是本病的致病因素，更是重要的病理产物，是本病发生发展、迁延难愈的关键。在治疗上提出以“益肾元、解肾毒”为大法，并根据不同兼夹辨证施治，采用药对，长治缓图。以“肾毒”立论拟定的经验方苏茵解毒方，在临床治疗和实验研究上均显示出明显的效果，并已制备成院内制剂临床使用，在疗效及经济效益方面均具有显著的优势。     

化浊解毒方对溃疡性结肠炎的治疗作用及机制

目的探讨化浊解毒方治疗溃疡性结肠炎(UC)的治疗作用及机制。方法120例UC患者按照随机数字表法分为观察组、对照组各60例。观察组予中药化浊解毒方口服,每日1剂,早晚2次温服;对照组予美沙拉嗪肠溶片口服,1.0 g/次,3次/d。2组疗程均4周。对比2组治疗前后Geboes指数、结肠镜下黏膜表现、生活质量评分、疾病活动指数及血清炎性因子IL-8、IL-35水平,凝血指标血清FIB水平,统计治疗后1年内复发情况。结果治疗后,观察组Geboes指数、疾病活动指数及血清炎性因子IL-8水平、凝血指标血清FIB水平均较本组治疗前降低,生活质量评分、血清炎性因子IL-35水平升高(P<0.05);且观察组治疗后疾病活动指数及血清炎性因子IL-8水平、凝血指标血清FIB水平均低于对照组,生活质量评分、血清炎性因子IL-35水平均高于对照组(P<0.05)。与对照组相比,治疗组糜烂、溃疡改善不明显(P>0.05),充血水肿、颗粒样变等肠镜表现改善情况均优于对照组(P<0.05)。治疗结束1年观察组复发率为10.64%,对照组为23.53%,2组差异有统计学意义(P<0.05)。结论化浊解毒方能改善UC患者临床症状,修复肠黏膜病理损伤,降低复发率;其机制可能与调节血清炎性因子IL-8、IL-35和凝血因子FIB水平有关。     

益气化瘀解毒方对MRP、GST-π和Topo Ⅱ基因在Sorafenib获得性耐药人肝癌QGY7702细胞表达的干预研究

目的探讨益气化瘀解毒方干预后对Sorafenib获得性耐药人肝癌QGY7702细胞(QGY7702/Sora)增殖及MRP、GST-π和Topo Ⅱ基因表达的影响。方法培养QGY7702/Sora细胞和QGY7702细胞,利用Cell Counting Kit-8(CCK-8)法检测Sorafenib对细胞的半数抑制率浓度(IC50值),计算耐药指数RI;观察益气化瘀解毒方对耐药细胞的增殖影响;采用荧光定量PCR检测药物干预前后2种细胞中MRP、GST-π和Topo Ⅱ基因表达水平。结果亲本细胞和耐药细胞Sorafenib的IC50值分别为(7.993±0.522)μmol/L和(19.651±1.216)μmol/L,RI约为2.5。益气化瘀解毒方可抑制耐药细胞的增殖活性。2种细胞的MRP、GST-π、Topo Ⅱ表达量无明显差异(P>0.05)。Sorafenib组可促进耐药细胞MRP 、GST-π基因的过表达(P<0.05),益气化瘀解毒方组可抑制GST-π基因的过表达(P<0.01),且联合Sorafenib可显著提高Topo Ⅱ基因的表达量(P<0.01)。结论 QGY7702/Sora细胞MRP、GST-π和Topo Ⅱ的表达水平与亲本细胞无显著差异。耐药细胞对Sorafenib敏感性降低与MRP、GST-π过表达相关,而益气化瘀解毒方拮抗Sorafenib耐药与抑制GST-π过表达相关。     

益气复智颗粒对多发脑梗死性痴呆模型大鼠脑组织细胞凋亡的影响

目的 观察益气复智颗粒对多发脑梗死性痴呆模型大鼠脑皮质形态学、细胞凋亡的影响。方法 采用颈内动脉注射血栓的方法，复制多发梗死性痴呆大鼠模型，观察益气复智颗粒12．42g/kg分别于手术前、手术前后、手术后灌胃对实验动物脑皮质形态学、细胞凋亡的影响。结果 益气复智颗粒能使脑缺血后脑内神经细胞凋亡数目下降。结论 益气复智颗粒具有较好的保护脑神经元，阻断脑缺血致神经细胞死亡病理过程的作用。     

HPLC法测定滑膜炎颗粒中原儿茶醛的含量

目的建立滑膜炎颗粒剂中原儿茶醛的含量测定方法质量。方法采用高效液相色谱法对方中原儿茶醛进行含量测定。结果高效液相色谱法测定结果表明原儿茶醛在0．1005～1．005μg范围内呈线性关系，平均加样回收率为99．22％；RSD为0．72％。结论本法简便，重现性好、结果可靠，可作为控制滑膜炎颗粒剂的质量方法。     

Distribution of glutathione and glutathione-related enzyme systems in mitochondria and cytosol of cultured cerebellar astrocytes and granule cells

The cellular and regional distribution of glutathione (GSH) and GSH-related enzyme systems involved in cellular defense against reactive oxygen species and electrophilic xenobiotics in the nervous system has been extensively studied. However, little is known about the subcellular distribution of GSH systems in brain tissue and cultured neural cells. The present study investigates the distribution of mitochondrial and cytosolic GSH and GSH-related enzymes in cultured cerebellar astrocytes and granule cells, and compares them with levels in the adult rat cerebellum. Cytosolic GSH levels and cytosolic activities of glutathione reductase (GR), glutathione peroxidase (GPx) and glutathione-S-transferase (GST) in astrocytes were 57, 153, 245, and 92% higher than those found in granule cells, respectively. In contrast, granule cells contained significantly higher mitochondrial GSH levels than astrocytes. Granule cells also demonstrated comparable mitochondria/cytosolic concentrations of GSH and GR, GPX and GST activities to those observed in the cerebellar tissue, whereas ratios in astrocytes were markedly lower. Although in vitro treatments with 100 μM ethacrynic acid depleted both cytosolic and mitochondrial GSH in cultured astrocytes and granule cells in a time-dependent fashion, cellular GSH in granule cells was more resistant to the GSH-depleting agent than astrocytes. These results suggest that although GSH and GSH-related enzymes are abundant in cytosolic compartments of astrocytes, mitochondrial pools are relatively small. Since brain mitochondria are sites of significant hydrogen peroxide generation, the mitochondrial localization of GSH and its associated enzymes in neural cells provide important defenses against toxic oxygen species in the nervous system. Differences in subcellular distribution of GSH systems in individual neural cell types may provide a basis for selective cellular and/or subcellular expression of neurotoxicity.     

Ultrastructural pathology and cytochemical investigations of l-2-chloropropionic acid-induced neurointoxication of the rat cerebellum

The objectives of the studies described were to assess the ultrastructural neuropathology, blood-brain barrier (BBB) integrity and calcium status of the cerebellum of rats following a single dose of 750 mg · kg^–1 l-2-chloropropionic acid (l-2-CPA). The first indications of intoxication appeared at 36 h when condensation of many granule cells associated with Purkinje cell degeneration and marked astroglial swelling were observed. Some electron-lucent granule cells were also noted lying amongst these condensed forms. Condensed granule cells had swollen, electron-lucent mitochondria, dilated Golgi apparatus and nuclear crenation. Occasionally, areas of granule cell necrosis were also present at this time. Granule cell condensation probably represents a preliminary and irreversible stage in an excitotoxic process that leads to necrosis. At 48 and 72 h, most granule cells were necrotic, and occasionally, extravasation of both erythrocytes and leucocytes into the expanded extravascular space was observed. Evaluation of the BBB by ultrastructural cytochemical visualisation of horseradish peroxidase injected i.v. 2 min before killing by perfusion fixation showed substantial leakage. At 36 h post-dose, ultrastructural calcium localisation using oxalate/pyroantimonate precipitation demonstrated a substantial increase in calcium pyroantimonate precipitate in mitochondria and other membranous cytoplasmic organelles (especially the Golgi apparatus) in condensed granule cells, but with little in their nuclei. However, their immediate neighbours (of ostensibly normal ultrastructural appearances) contained greater amounts of intranuclear precipitate. Swollen astroglial cells (especially the Bergmann glia) contained considerable quantities of precipitate. A possible excitotoxic mechanism via l-2-CPA-induced NMDA receptor agonism leading to overwhelming calcium influx and disruption of cellular calcium homeostasis is proposed. Received: 8 May 1996 / Revised: 1 September 1996 / Accepted: 11 September 1996     

保肝解毒胶囊对雷公藤多甙片所致小鼠急性肝损伤保护作用的实验研究

目的：运用新建雷公藤多甙致小鼠急性肝损伤模型，探讨保肝解毒胶囊对该模型肝损伤保护作用的效果和机理。方法：连续5d给小鼠灌服保肝解毒胶囊制剂，而后以雷公藤多甙片造小鼠急性肝损伤模型，检测小鼠血清谷丙转氨酶(ALT)、谷草转氨酶(AST)、还原型谷胱甘肽(GSH-Px)、超氧化物歧化酶(SOD)，肝匀浆中过氧化物(LPO)含量，并取肝组织作病理检查。结果：保肝解毒胶囊可以对抗肝损伤，其疗效和剂量有关；保肝解毒胶囊保护肝细胞的机理与对抗脂质过氧化反应有关。结论：保肝解毒胶囊具有保护肝脏的作用，     

大鼠创伤性肠粘连模型的制备及黄厚排气颗粒对其粘连程度的影响

为筛选出操作方法简便，结果稳定可控的大鼠创伤性肠粘连模型，观察中药复方黄厚排气颗粒对其粘连程度的影响，选用SD大鼠，手术造成肠粘连模型，用中药复方2．5、5．0、10．0g/kg连续治疗7d后观察肠粘连程度。结果表明，以盲肠型动物模型的制备较为理想，手术易于操作，结果稳定可控。用中药复方治疗后模型动物的肠粘连程度得到明显改善。提示黄厚排气颗粒对术后肠粘连有一定的预防作用。     

养阴清热、宣痹通络法治疗类风湿性关节炎的临床研究

目的 观察清络通痹颗粒治疗类风湿性关节炎阴虚络热证的临床疗效。方法 将118例患者随机分为清络通痹颗粒治疗组63例和雷公藤多甙片对照组55例，观察用药前后主要症状、体征和实验室检测指标的变化。结果 治疗组的临床治愈率为9．52％，临床治愈显效率为38．10％，总有效率为90．48％，疗效明显优于对照组的0％、20％、83．64％（P＜0．05）；治疗组的类风湿因子滴度、血沉、C反应蛋白、免疫球蛋白也明显降低，与对照组相比差异显著（P＜0．05或P＜0．01）。结论 清络通痹颗粒具有抗炎镇痛、调节免疫紊乱等作用，从而达到控制病情的治疗效果。