Bromocriptine protects perilesional spinal cord neurons from lipotoxicity after spinal cord injury

Recent studies have revealed that lipid droplets accumulate in neurons after brain injury and evoke lipotoxicity,damaging the neurons.However,how lipids are metabolized by spinal cord neurons after spinal cord injury remains unclear.Herein,we investigated lipid metabolism by spinal cord neurons after spinal cord injury and identified lipid-lowering compounds to treat spinal cord injury.We found that lipid droplets accumulated in perilesional spinal cord neurons after spinal cord injury in mice.Lipid droplet accumulation could be induced by myelin debris in HT22 cells.Myelin debris degradation by phospholipase led to massive free fatty acid production,which increased lipid droplet synthesis,β-oxidation,and oxidative phosphorylation.Excessive oxidative phosphorylation increased reactive oxygen species generation,which led to increased lipid peroxidation and HT22 cell apoptosis.Bromocriptine was identified as a lipid-lowering compound that inhibited phosphorylation of cytosolic phospholipase A2 by reducing the phosphorylation of extracellular signal-regulated kinases 1/2 in the mitogen-activated protein kinase pathway,thereby inhibiting myelin debris degradation by cytosolic phospholipase A2 and alleviating lipid droplet accumulation in myelin debris-treated HT22 cells.Motor function,lipid droplet accumulation in spinal cord neurons and neuronal survival were all improved in bromocriptine-treated mice after spinal cord injury.The results suggest that bromocriptine can protect neurons from lipotoxic damage after spinal cord injury via the extracellular signal-regulated kinases 1/2-cytosolic phospholipase A2 pathway.

Effect of Chinese Herbs Bu-shen on Expression of Pituitary PRL-R and PrRP-R in the Bromocriptine-induced Hypoprolactin Rat Abortion Model

Objective To study the effect of Chinese herbs preparation Bu-shen on pituitary prolactin-releasing peptide receptor (PrRP-R) and prolactin receptor (PRL-R) expression in the bromocriptine-induced rat abortion model Materials & Methods Female SD rats were divided into five groups randomly. Group A,B,C and D were injected with bromocriptine [0. 3 mg/(kg · d)] during the pregnant day 6～ 8, respectively. Group B was given powder of Bu-shen herbs [3 g/(kg · d)]. Group C was injected with prolactin (8 IU) twice a day and Group D with progesterone [(8 mg/kg · d) in the pregnant day 1～ 11. The rats in Group E were normal pregnant rats. All these rats were killed at the pregnant day 12 to observe the expression of PrRP-R, PRL-R from the pituitary using RT-PCR. Results The pregnant rate and total number of litters in Group A were significantly lower than those in Group B, C, D and E (P＜0. 01) and the expression of PrRP-R and PRL-R in the pituitary of Group A was higher than that of any other group. Conclusion Preparation Bu-shen plays a regulatory role in the secretion of prolactin possibly via modulating rats' hypothalamus and pituitary.

Hormone Secretion by Cell Culture of Human GH-PRL Secreting Pituitary Adenomas: Effects of Bromocriptine

Dopamine agonists effectively reduce the secretion of prolactin (PRL) in the great majority of prolactinomas and reduce the bulk of the adenomas, as well as have partial therapeutic effect on some patients with acromegaly. The inhibitory effect of bromocriptine (BC), a dopamine agonist, on growth hormone (GH) and PRL secretion of dispersed cells from the pituitary adenomas of 16 cases of acromegaly, which secret GH and PRL simultaneously, were evaluated in vitro. The significant inhibitory effects of BC on PRL secretion were found in 12 cases. It was also found that PRL secretion was strongly inhibited when GH was suppressed; on the contrary, when GH secretion was not suppressed, the production of PRL was not or weakly inhibited. The exact mechanism of the effects is nuclear so far. It is necessary to investigate, at molecular level, the etiology of GH-PRL adenomas and its response to therapeutic agents.

Auditory evoked potentials recorded in monkeys with hallucinatory-like behaviors induced by bromocriptine

Objective Bromocriptine and other dopamine D2 receptor agonists can affect a range of behaviors in nonhuman primates, particularly those behaviors associated with motor and mental function, such as suppressant behaviors and hallucinatory-like behaviors in monkeys. Besides bromocriptine, the dysfunction of the rapid eye movement sleep （REM） mechanism may also contribute to hallucinations. Dissociation of wakefulness, REM, and non-REM （NREM） can cause a series of psychotic symptoms. Methods In present study, we simultaneously recorded auditory evoked potentials （AEP） from five cerebral regions in monkeys during normal and psychotomimetic states to investigate and compare state-dependent changes in AEE Results Phase reversal of peak-to-baseline amplitude of 250 ms component （PBA250） in dorsolateral prefrontal cortex was common characteristic of hallucinatory-like and REM, and that hallucinatory-like and REM shared the equivalent modulatory orderliness of the PBA250 in dorsolateral prefrontal cortex. This result suggests that hallucinatory-like and REM share an equivalent electrophysiological modulatory in dorsolateral prefrontal cortex. Conclusion Our results reveal that emergence of the N250 in dorsolateral prefrontal cortex is an exclusive marker that may help to discern whether hallucinatory-like behaviors is exhibited, which suggests that dorsolateral prefrontal cortex may be the most pivotal region for exhibition of hallucinatory-like behaviors.

Synergistic effect of bromocriptine and tumor necrosis factor-a on reversing hepatoceiiuiar carcinoma multidrug resistance in nude mouse MDRl model of liver neoplasm

AIM： To investigate the effect of bromocripUne （BCT） and tumor necrosis factor-α ClNF-α） on hepatocellular carcinoma （HCC） multidrug resistance （MDR） in nude mouse HDR model of liver neoplasm. METHODS： Human hepatocarcinoma cell line HepG2t drug resistant hepatocarcinoma cell line HepG2/adriamycin （ADM） and hepatocarcinoma cell line transfected with TNF-α gene HepG2JADM/TNF were injected into the liver of nude mice via orthotopic implantation and MDR model of liver neoplasm in vivo was established （HepG2t ADM, TNF, BCT groups）. Among these groups, BCT group and TNF group were treated with BCT through gastric canal. Each group was divided into control group and chemotherapy group. Size and weight of the tumor were measured. Furthermore, tumor his^logical character and growth of the nude mice were observed and their chemosensitivity was tested. MDR-associated genes and proteins （MRP, LRP） of implanted tumors were detected by immunohistochemistry, reverse transcriptase polymerase chain reaction, and apoptosis rate of hepatocarcinoma cells was detected by TUNEL assay. RESULTS： The nude mouse model of each cell line was inoculated successfully. The tumor growth rate and weight were significantly different among groups. After chemotherapy, abdominal cavity tumor growth inhibition rate was higher in BCT group （67%） compared to ADM and TNF groups, and similar to HepG2group （54%）. MDRI and LRPmRNA could be detected in all groups, but TNF-α was detected only in TNF and BCT groups. Furthermore, MDR1 and LRP protein expression of tumors in TNF and BCT groups was low similar to HepG2 group. The apoptosis rate of hepatocarcinoma cells was much higher in BCT group than in other groups with TUNEL assay. CONCLUSION： BCT and TNF-a can reverse HCC MDR in nude mouse MDR1 model of liver neoplasm. 2005 The WJG Press and Elsevier Inc. All rights reserved

Uncontrolled central hyperthermia by standard dose of bromocriptine:A case report

BACKGROUND Some patients present to the intensive care unit due to noninfectious pathologies resulting in fever,especially acute neurological injuries,including brain trauma and intracranial haemorrhage.The cause has been identified to be central hyperthermia characterized by a high core temperature and a poor response to antipyretics and antibiotics.However,no proper guidelines on how to treat central hyperthermia have been developed for clinical practice.CASE SUMMARY A 63-year-old woman was transferred to our hospital due to injury after a traffic accident.Eight hours after admission,her pupils enlarged bilaterally from 2.5 mm to 4.0 mm.She developed severe coma and underwent decompressive craniectomy.She was diagnosed with central hyperthermia after surgery and was prescribed bromocriptine.The standard dose of bromocriptine could not control her hyperpyrexia,and we prescribed 30 mg a day to control her temperature.CONCLUSION Bromocriptine may be effective in controlling central hyperthermia and have a dosage effect.

Bromocriptine in Central Hyperthermia after Severe Traumatic Brain Injury

Strong evidence showed that fever after traumatic brain injury TBI is associated with increased mortality. In this study, we tried to evaluate the role of Bromocriptine in central hyperthermia in patients with severe TBI. This prospective controlled study was conducted on 50 severe TBI patients who admitted to the critical care department and confirmed on Computed Tomography (CT) of the brain and GCS of less than 9 at admission. Then, they were randomly assigned into 2 groups. Bromocriptine group (25) received bromocriptine 7.5 mg/day during 24 hours from admission through a naso-gastric (NG) feeding tube. Control group (25) received conventional treatment only. Temperature was measured every 2 hours. The antipyretic measures used were the same across all patients enrolled. The primary outcome was number of patients diagnosed with central hyperthermia. After the discharge of all patients, there was a statistically significant difference between the 2 groups in number of patients diagnosed with central hyperthermia (6 (24%) in bromocriptine group Vs 18 (72%) in control, p = 0.002). There were no differences in hospital length of stay (p = 0.904) or mortality (p = 0.393). Early administration of bromocriptine in severe TBI may be associated with lower incidence of central hyperthermia with no effect on length of stay or mortality.

Sex-related changes in tumor consistency in prolactinoma patients after bromocriptine pretreatment

Objective It has long been reported that prolactinomas treated with bromocriptine increase fibrosis and may affect surgical outcomes.We retrospectively studied 238 consecutive patients with histopathologically confirmed prolactinomas undergoing microsurgery in a single neurosurgery department of Tongji Hospital(Wuhan,China) from 2012 to 2015 in order to evaluate tumor consistency changes after bromocriptine pretreatment and surgical outcomes.Methods We divided the patients into four groups;males in the dopamine agonist(DA) group,females in the DA group,males in the no DA group,and females in the no DA group,and we compared the surgery process,specimen Masson staining,and clinical outcomes of the four groups.According to a previously published classification,the operative notes from an experienced neurosurgeon were reviewed to classify the consistency of tumors as "fibrous" or "nonfibrous".Results No differences in tumor consistency were found in male patients with or without DA treatment.However,in female patients with DA treatment,tumors were likely to be harder in texture than the tumors of female patients without DA treatment.Despite tumor consistency differences between sexes,the tumor biological remission rate was similar between groups,as was the rate of tumor resection.Discussion Our study indicates that preoperative DA therapy impacts tumor consistency in female patients but not male patients.Although the surgical and histopathological outcomes are not influenced,these findings may provide useful information for the choice of operative approach and surgery process for pituitary adenoma.

Bromocriptine enhances the uptake of^(99m)Tc-MIBI in patients with hepatocellular carcinoma

99mTc-methoxyisobutyl isonitrile （MIBI） is a suitable transport substrate for the multidrug resistance gene prod- uct P-glycoprotein （P-gp） and widely used for tumor imaging. Bromocriptine has been shown to inhibit the ATPase activity and the function of P-gp. We hypothesized that bromocriptine could promote the accumulation of MIBI by inhibiting P-gp activities, a feature that can be taken advantage of for enhancing 99mTc-MIBI imaging. In the cur- rent study, we sought to investigate whether bromocriptine enhanced the uptake of 99mTc-MIBI in hepatocellular carcinoma patients. Sixty primary hepatocellular carcinoma patients received 99mTc-MIBI single photon emission computer tomgraphy （SPECT） prior to surgery. 99mTc-MIBI SPECT was performed 15 and 120 min after injec- tion of 20 mCi 99mTc-MIBI, and early uptake, delayed uptake （L/Nd）, and washout rate （L/Nwr） of 99mTc-MIBI were obtained. In addition, a second 99mTc-MIBI SPECT was performed according to the same method 48 h after bromocriptine administration. We found that, prior to bromocriptine administration, significant MIBI uptake in tumor lesions was noted in only 10 （16.7%, 10/60） patients with hepatocellular carcinoma. No significant MIBI uptake was observed in the tumor lesions of the remaining 50 （83.3%, 50/60） hepatocellular carcinoma patients. Following bromocriptine administration, all the patients without apparent MIBI uptake demonstrated significant MIBI uptake on 99mTc-MIBI SPECT （P 〈 0.05）. Our findings indicate that bromocriptine enhances the uptake of 99mTc-MIBI in patients with hepatocellular carcinoma.

Effect of Bromocriptine on Insulin Resistance in Patients with PCO

Introduction: Poly cystic ovary (PCO) is one of the most common endocrine disorders in women. All patients with PCO are at risk of insulin resistance, IFG and diabetes. Recently, bromocriptine is used in treatment of diabetes mellitus type II to improve insulin resistance. Objective: The aim of this study is the evaluation of bromocriptine on insulin resistance in PCO people. Patients and Methods: In this single-blind controlled clinical trial with placebo, 44 patients with PCO referring to endocrinology clinic were evaluated. Inclusion criteria were BMI > 25 kg/m2 and diagnosed PCO patients according to Rotterdam criteria and rule out other causes. Blood samples were obtained for FBS, Fasting Insulin, Prolactin, TSH and 17(OH)P. They divided two groups: Case group was given bromocriptine 2.5 mg daily and placebo was given to control group. Patients were treated for 8 days and in day 9th blood sample was obtained for FBS, Fasting insulin, HOMA-IR index. Mann-Whitney method is used for mean comparison. Results: Data analysis using showed in pre diabetes range, mean changes of FBS, insulin level and IR in Groups 1 and 2 had significant differences(P = 0.004), but no significant different was found in FBS < 100 mg/dl (P = 0.92). In group with BMI 2, no significant differences were found in changes in FBS < insulin level and IR (P = 0.13, 0.13, and 0.11 respectively). In group with BMI ≥ 30 kg/m2, no significant differences were found in changes in insulin level and IR (P = 0.69, 0.089 respectively). Mean systolic blood pressure changes in Group 1 and 2 in FBS > 100 mg/dl with (P = 0.036) were significant, but no significant difference showed in mean change of diastolic blood pressure in FBS > 100 mg/dl (P = 0.99). In FBS < 100 mg/dl mean changes in systolic and diastolic blood pressures were not significant (P = 0.6). Age showed no difference changes in effect on treatment in Groups 1 and 2 (P = 0.1). Conclusion: Our study showed, even in the short-term consumption, bromocriptine reduced FBS and insulin levels and insulin resistance in PCO patients with pre-diabetes range.

Effect of Chinese Herbs Bu-shen on PRLR, PR, ER mRNA of Decidue in Bromocriptine-induced Hypoprolac- tin Rat Abortion Model

Objective To explore the effect of Chinese herbs on PRLR, PR, ER mRNA of decidue in Bromocriptine-induced hypoprolactin abortion rat model from gene transcription level, and observe the changes of blood PRL, P, E2.Methods RT-PCR method was taken to analyses the differences of PRLR, PR, ER mRNA in decidue between model group (A group) and model + herbs group (A + H group); RIA was taken to measure the serum levels of PRL, P, E2. Results PRLR, PR mRNA expression in decidue of Group A was significantly lower than the A + H group (P<0. 01) , no difference in ER mRNA expression (P>0. 05); the abortion rate of Group A was 67 %, Group A+H was 17% , the difference was significant; as for the PRL and P level of day 7-1.0, the A group was significantly lower than the A+H group (P<0. 05).Conclusion Bromocriptine could induce abortion by declining the blood PRL, P level and downregulating PRLR, PR mRNA expression in decidue. Chinese herbs might maintain pregnancy by promoting PRL, P secretion and upregulating PRLR, PR mRNA expression in decidue.

开郁醒神法对高催乳素血症患者卵巢动脉血流参数的影响

目的:观察开郁醒神法治疗高催乳素血症的临床疗效。方法:将60例肝郁肾虚型高催乳素血症患者随机分为对照组和观察组,每组30例。对照组采用甲磺酸溴隐亭片治疗,观察组给予开郁醒神法中药治疗。比较两组患者治疗前后的血清泌乳素(Prolactin,PRL)、促卵泡生成素(Follicle-stimulating Hormone,FSH)、黄体生成素(Luteinizing Hormone,LH)、雌二醇、孕酮、睾酮,以及卵巢的血管化指数(Vascularization Index,VI)、血流指数(Flow Index,FI)和血管化血流指数(Vascularization Flow Index,VFI)等指标,并比较中医证候评分,评价疗效。结果:治疗后,两组患者的PRL水平均明显下降(P<0.05),且观察组改善优于对照组(P<0.05)。治疗后,对照组患者的FSH、LH、雌二醇、孕酮和睾酮水平无明显变化(P>0.05),观察组患者FSH、LH水平明显下降,雌二醇水平显著升高(P<0.05),且观察组改善优于对照组(P<0.05)。观察组孕酮和睾酮水平无明显变化(P>0.05)。治疗后,对照组患者卵巢VI、FI和VFI水平无明显变化(P>0.05),观察组患者卵巢VI、FI和VFI水平均显著升高(P<0.05),且升高优于对照组(P<0.05)。治疗后,对照组中医证候评分水平略有下降,但组内差异无统计学意义(P>0.05);观察组中医证候评分水平显著下降(P<0.05),且下降优于对照组(P<0.05)。观察组总有效率高于对照组,组间差异有统计学意义(P<0.05)。结论:开郁醒神法中药可以显著降低高催乳术血症患者PRL、FSH和LH水平,纠正紊乱的垂体功能;提高雌二醇水平,恢复卵巢分泌功能;还可以显著提高卵巢动脉VI、FI和VFI水平,改善卵巢动脉血流灌注;并能显著降低中医证候评分水平,舒缓临床证候,显著提高治疗有效率。

3种流产剂对大鼠妊娠干预作用的比较研究

为研究米非司酮、溴隐亭和脂多糖3种流产剂对SD大鼠妊娠的影响。通过有无阴栓和阴道分泌物涂片确定SD大鼠是否妊娠,并将妊娠大鼠随机分为空白对照组、米非司酮组、溴隐亭组和脂多糖组。空白对照组于妊娠6~8 d皮下注射生理盐水,其余各组皮下注射相应流产剂,建立流产模型。于妊娠12 d观测各组流产率、血液生化指标,ELISA检测炎性细胞因子和孕激素水平,苏木精-伊红染色法(hematoxylin-eosin staining,HE)染色检测肝脏及子宫组织的病理学变化。结果显示,空白对照组、米非司酮组、溴隐亭组和脂多糖组的流产率分别为0、100%、50%和33.3%;与空白对照组相比,各流产剂致流产模型组大鼠子宫连胎重、孕激素水平均显著降低(P<0.05),TNF-α、IL-2、IL-12、IL-6、IL-1β水平均显著增加(P<0.05),且均会对肝、肾、子宫组织造成不同程度的代谢和病理性损伤;与空白对照组相比,各组核因子-κB(nuclear factor-kappa B,NF-κB)p65的表达更为强烈,雌激素受体(estrogen receptor,ER)表达水平降低。表明溴隐亭用于致流产的效果优于米非司酮和脂多糖,对母体损伤小。

补肾益气清热方对溴隐亭致大鼠流产模型中垂体PRL-R、PrRP-R表达的影响

目的 :探讨补肾益气清热中药对溴隐亭致 SD大鼠流产模型中垂体 PRL- R、Pr RP- R表达的影响。方法 :将 SD孕大鼠随机分 5组 :其中 A～ D组在孕 6～ 8d皮下注射溴隐亭 0 .3mg/( kg· d) ,A组为模型组 ,B组、C组、D组孕 1～ 1 1 d分别灌胃中药粉剂 3g/( kg· d)、注射外源性 PRL 8IU/次 (每天 1 2 :0 0和 2 4 :0 0 ,bid)、黄体酮 8mg/( kg·d) ;E组为正常妊娠组。所有动物于孕 1 2 d处死 ,取垂体 ,用 RT- PCR方法测各组大鼠垂体 Pr RP- R、PRL- R的表达。结果 :B组、C组、D组的妊娠率与 A组相比 ,差异有显著性 ( P<0 .0 1 ) ,B组妊娠率与 C组、D组、E组相比差异无显著性。 A组垂体 Pr RP- R、PRL- R的表达明显高于其它各组 ( P<0 .0 5 )。结论 :补肾益气清热中药可能通过机体的整体调节并作用于下丘脑、垂体 ,影响

甲磺酸溴隐亭联合人绒毛膜促性腺激素治疗高泌乳素血症的临床效果及对激素水平的影响

目的 观察甲磺酸溴隐亭联合人绒毛膜促性腺激素治疗高泌乳素血症的临床效果及对患者激素水平的影响。方法 将2022年1月至2023年9月武义县第一人民医院妇产科收治的144例高泌乳素血症患者以随机数字表法分为观察组、对照组,每组72例,对照组口服甲磺酸溴隐亭片治疗,观察组患者口服甲磺酸溴隐亭片治疗的同时联合人绒毛膜促性腺激素治疗,比较两组临床疗效、治疗前后血清泌乳素及黄体生成激素、雌二醇等激素水平变化、女性性功能指数(FSFI)及贝克忧郁量表第2版(BDI-Ⅱ)评分变化、患者停药3个月与6个月后疾病复发率情况以及不良反应发生情况。结果 对照组与观察组总有效率分别为86.11%、97.22%,差异有统计学意义(χ^(2)=4.455,P<0.05);治疗后,观察组血清泌乳素为(24.38±5.52)μg·L^(-1),低于对照组(28.65±4.92)μg·L^(-1),黄体生成激素、雌二醇等激素水平分别为(20.99±2.15) pg·m L^(-1)、(53.84±7.23) IU·L^(-1),均高于对照组(18.54±2.55) pg·m L^(-1)、(49.63±8.23) IU·L^(-1),差异有统计学意义(t=4.900、6.233、3.261,均P<0.001);观察组治疗后FSFI评分为(32.12±1.85)分,高于对照组(28.54±3.25)分,BDI-Ⅱ评分为(8.76±0.62)分,低于对照组(10.34±0.85)分,差异有统计学意义(t=8.123、12.743,均P<0.001);对照组(4.17%)与观察组(2.78%)患者不良反应发生率相近,差异无统计学意义(χ^(2)=0.000,P>0.05);对照组停药3个月疾病复发率为5.56%,高于观察组(0),但差异无统计学意义(χ^(2)=2.314,P>0.05);对照组停药6个月疾病复发率为8.33%,高于观察组(0),差异有统计学意义(χ^(2)=4.348,P<0.05)。结论 甲磺酸溴隐亭与人绒毛膜促性腺激素联合治疗高泌乳素血症临床效果显著,可改善患者激素水平及性功能、不良心理,且停药后患者疾病复发率低,不良反应少。

基于症状改善及实验室检测评价乳痈消方治疗肿块期非哺乳期乳腺炎的研究

目的研究乳痈消方治疗肿块期非哺乳期乳腺炎(NPM)对患者症状和实验室检测指标的改善效果。方法以2020年8月—2022年4月浙江中医药大学附属丽水中医院收治的88例肿块期NPM患者随机分为西药组(44例)和联合中药组(44例)。西药组采用甲磺酸溴隐亭进行治疗,联合中药组在西药组的基础上采用乳痈消方进行治疗,两组均治疗4周。统计两组治疗4周后的疗效,比较两组治疗前和治疗4周后症状体征积分、实验室检测指标、炎症指标。结果治疗4周后,联合中药组总有效率高于西药组(P<0.05)。治疗4周后与治疗前比较,两组乳房脓肿、乳房肿物、乳房瘘管、乳房红肿、乳房疼痛、乳头凹陷评分及血清免疫球蛋白A(IgA)、总补体(TC)、白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)、C反应蛋白(CRP)、外周血白细胞(WBC)、中性粒细胞(N)、自然杀伤细胞(NK)水平降低,联合中药组乳房脓肿、乳房肿物、乳房瘘管、乳房红肿、乳房疼痛、乳头凹陷评分及血清TC、IL-6、TNF-α、CRP、外周血WBC、N、NK水平低于西药组(P<0.05)。治疗4周后与治疗前比较,两组外周血CD_(4)^(+)水平升高,联合中药组高于西药组(P<0.05)。结论乳痈消方治疗肿块期NPM,可有效改善患者症状及实验室指标,调节机体免疫功能,降低机体炎症反应,具有较好的治疗效果。

乳腺癌PRL-R表达阳性随年龄变化规律探究

目的 探讨乳腺癌原发灶PRL-R表达阳性随年龄变化的规律。方法 收集中山大学肿瘤防治中心行手术治疗的129例乳腺癌患者,中位年龄46岁。采用免疫组化法配合单克隆抗体检测各病例术后原发灶标本蜡块中PRL-R的表达状况,并分析PRL-R表达阳性随患者年龄的变化规律。结果 129例患者中PRL-R阳性表达88例,阳性率68.2%。以每5岁作亚单元计算PRL-R阳性率的结果显示出35岁和55岁两个重要变化节点,以此两个年龄节点将129例患者分成年龄递进三个亚组,Spearsman秩相关分析显示出PRL-R表达阳性与年龄增长总体呈负相关（r=-0.183,P〈0.05）,且36~55岁组患者PRL-R阳性率高于〉55岁组患者（2=8.016,P=0.005）。结论 总体上PRL-R表达阳性与患者年龄增长呈负相关,其变化规律大致为：35岁后PRL-R表达阳性率可见增高趋势,然后于55岁左右又快速降至较低水平。

垂体腺瘤出血性卒中的危险因素分析

目的 探讨影响垂体腺瘤出血性卒中发生的危险因素。方法 回顾性分析青岛大学附属医院神经外科2010年1月—2021年1月收治的875例无功能垂体腺瘤患者的临床资料,并按照有无垂体腺瘤出血性卒中发生分为卒中组(88例)与非卒中组(787例),采用单因素分析及多因素Logistic回归分析筛选影响垂体腺瘤出血性卒中发生的危险因素。结果 卒中组患者中,抗栓药物治疗史、肿瘤复发或残留、有介入手术或介入造影史的比例均明显高于非卒中组,微腺瘤的比例明显低于非卒中组,差异均有统计学意义(P<0.05)。多因素Logistic回归分析提示,大腺瘤(OR=0.189,95%CI:0.069~0.522,P=0.001)、抗栓药物治疗史(OR=4.168,95%CI:1.611~10.785,P=0.003)、溴隐亭治疗(OR=2.912,95%CI:1.156~7.34,P=0.023)、肿瘤复发或残留(OR=2.787,95%CI:1.179~6.59,P=0.020)是垂体腺瘤出血性卒中的独立危险因素。结论 存在大腺瘤、抗栓药物治疗史、溴隐亭治疗、肿瘤复发或残留等情况的垂体腺瘤患者较易发生垂体腺瘤出血性卒中。

抗精神药物致肉芽肿性乳腺炎5例病例分析

目的:探索服用抗精神类药物所致的肉芽肿性乳腺炎的发病机制及治疗方案。方法:选取5例服用抗精神类药物期间发生肉芽肿性乳腺炎的病例,通过对5位患者血清泌乳素的变化、乳腺肿块大小、治疗方式和周期及愈后复发情况的分析,查阅相关研究成果,探索抗精神类药物与肉芽肿性乳腺炎的相关性,进一步研究抗精神类药物导致肉芽肿性乳腺炎的潜在发病机制,结合病因病机,进一步探索中医药治疗方案。结果:服用抗精神类药物所致的肉芽肿性乳腺炎不同于普通型肉芽肿性乳腺炎,前者特点为初发时泌乳素偏高、乳腺肿块较大,治疗期间泌乳素易反复升高,手术治疗切除范围较大,所需治疗周期较长,且预后易复发。在治疗方面,参考相关治疗方法,静脉应用糖皮质激素冲击缩短病程、抗生素药物抗感染、参芪扶正注射液扶正治疗,同时予以口服疏肝理气中草药,针对不同时期扩展中医外治法的应用,必要时采用手术治疗,5例患者的临床疗效显著。结论:长期服用抗精神药物,可刺激泌乳素分泌,致高泌乳血症,更有可能诱发肉芽肿性乳腺炎,但具体机制有待进一步探讨,因此应密切观测泌乳素,防范肉芽肿性乳腺炎的发生,中西医结合治疗此类疾病有更好的疗效和安全性。

基于Akt/mTOR信号通路探究芍药甘草汤和生麦芽对高泌乳素血症的作用机制

目的:分别考察生麦芽、芍药甘草汤对高泌乳素血症(HPRL)大鼠血清泌乳素相关激素水平及乳腺组织病理形态的影响,以及对乳腺组织p-Akt、p-mTOR、LC3等蛋白表达水平的影响。方法:随机取8只大鼠作为正常组,32只大鼠皮下注射甲氧氯普胺制备高泌乳素血症模型。造模成功的32只大鼠随机分为模型组、芍药甘草汤组、生麦芽组和溴隐亭组,每组8只。各药物组大鼠灌胃给予相应药物,正常组和模型组大鼠给予等体积蒸馏水,连续给药30 d。采用酶联免疫吸附法(ELISA)测定大鼠血清中泌乳素(PRL)、促黄体生成素(LH)、雌二醇(E2)、孕酮(Pg)、促卵泡素(FSH)含量;采用苏木精-伊红(HE)染色观察大鼠乳腺组织病理形态变化;蛋白免疫印迹法(Western blotting)及免疫组化(IHC)检测大鼠乳腺组织p-Akt、p-mTOR、LC3等蛋白表达水平。结果:模型组大鼠血清PRL水平明显高于正常组(P<0.01),血清LH、FSH、Pg和E2水平明显低于正常组(P<0.01);芍药甘草汤组、生麦芽组、溴隐亭组大鼠血清PRL水平明显低于模型组(P<0.01);芍药甘草汤组大鼠血清FSH、Pg水平明显高于模型组(P<0.05或P<0.01);生麦芽组大鼠血清FSH、Pg和E2水平明显高于模型组(P<0.05或P<0.01);溴隐亭组大鼠血清LH、FSH、Pg和E2水平明显高于模型组(P<0.05或P<0.01)。HE染色结果显示模型组大鼠乳腺增生,小叶数量、腺泡数量明显多于正常组,小叶体积大于正常组,并出现腺泡和导管扩张;芍药甘草汤组、生麦芽组和溴隐亭组大鼠乳腺增生情况均得到改善,乳腺小叶数量、腺泡和导管增生明显少于模型组。Western blotting检测结果显示,模型组大鼠乳腺组织中p-Akt和p-mTOR蛋白相对表达量及LC3-Ⅱ/Ⅰ高于正常组(P<0.01);芍药甘草汤组、生麦芽组和溴隐亭组大鼠乳腺组织中p-Akt和p-mTOR蛋白相对表达量及LC3-Ⅱ/Ⅰ均低于模型组(P<0.01)。IHC检测结果显示,模型组大鼠乳腺组织中Akt、p-Akt、mTOR、p-mTOR、LC3蛋白表达水平明显高于正常组(P<0.05或P<0.01);芍药甘草汤组、生麦芽组、溴隐亭组大鼠乳腺组织中p-Akt、p-mTOR、LC3蛋白表达水平明显低于模型组(P<0.05或P<0.01);芍药甘草汤组、溴隐亭组大鼠乳腺组织中mTOR蛋白表达水平明显低于模型组(P<0.05)。结论:芍药甘草汤、生麦芽能够有效降低高泌乳素血症大鼠血清泌乳素水平,抑制乳腺组织增生,其机制可能与减轻大鼠乳腺组织中自噬作用有关。